45 results on '"Kerchner, G"'
Search Results
2. Establishing Clinically Meaningful Change on Outcome Assessments Frequently Used in Trials of Mild Cognitive Impairment Due to Alzheimer’s Disease
- Author
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Lansdall, Claire J., McDougall, F., Butler, L. M., Delmar, P., Pross, N., Qin, S., McLeod, L., Zhou, X., Kerchner, G. A., and Doody, R. S.
- Published
- 2023
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3. Thirty-Six-Month Amyloid Positron Emission Tomography Results Show Continued Reduction in Amyloid Burden with Subcutaneous Gantenerumab
- Author
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Klein, Gregory, Delmar, P., Kerchner, G. A., Hofmann, C., Abi-Saab, D., Davis, A., Voyle, N., Baudler, M., Fontoura, P., and Doody, R.
- Published
- 2021
- Full Text
- View/download PDF
4. New insights into the genetic etiology of Alzheimer's disease and related dementias
- Author
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Bellenguez, C., Küçükali, F., Jansen, I. E., Kleineidam, L., Moreno-Grau, S., Amin, N., Naj, A. C., Campos-Martin, R., Grenier-Boley, B., Andrade, V., Holmans, P. A., Boland, A., Damotte, V., van der Lee, S. J., Costa, M. R., Kuulasmaa, T., Yang, Q., de Rojas, I., Bis, J. C., Yaqub, A., Prokic, I., Chapuis, J., Ahmad, S., Giedraitis, V., Aarsland, D., Garcia-Gonzalez, P., Abdelnour, C., Alarcón-Martín, E., Alcolea, D., Alegret, M., Alvarez, I., Álvarez, V., Armstrong, N. J., Tsolaki, A., Antúnez, C., Appollonio, I., Arcaro, M., Archetti, S., Pastor, A. A., Arosio, B., Athanasiu, L., Bailly, H., Banaj, N., Baquero, M., Barral, S., Beiser, A., Pastor, A. B., Below, J. E., Benchek, P., Benussi, L., Berr, C., Besse, C., Bessi, V., Binetti, G., Bizarro, A., Blesa, R., Boada, M., Boerwinkle, E., Borroni, B., Boschi, S., Bossù, P., Bråthen, G., Bressler, J., Bresner, C., Brodaty, H., Brookes, K. J., Brusco, L. I., Buiza-Rueda, D., Bûrger, K., Burholt, V., Bush, W. S., Calero, M., Cantwell, L. B., Chene, G., Chung, J., Cuccaro, M. L., Carracedo, Á., Cecchetti, R., Cervera-Carles, L., Charbonnier, C., Chen, H. -H., Chillotti, C., Ciccone, S., Claassen, J. A. H. R., Clark, C., Conti, E., Corma-Gómez, A., Costantini, E., Custodero, C., Daian, D., Dalmasso, M. C., Daniele, A., Dardiotis, E., Dartigues, J. -F., de Deyn, P. P., de Paiva Lopes, K., de Witte, L. D., Debette, S., Deckert, J., del Ser, T., Denning, N., Destefano, A., Dichgans, M., Diehl-Schmid, J., Diez-Fairen, M., Rossi, P. D., Djurovic, S., Duron, E., Düzel, E., Dufouil, C., Eiriksdottir, G., Engelborghs, S., Escott-Price, V., Espinosa, A., Ewers, M., Faber, K. M., Fabrizio, T., Nielsen, S. F., Fardo, D. W., Farotti, L., Fenoglio, C., Fernández-Fuertes, M., Ferrari, R., Ferreira, C. B., Ferri, E., Fin, B., Fischer, P., Fladby, T., Fließbach, K., Fongang, B., Fornage, M., Fortea, J., Foroud, T. M., Fostinelli, S., Fox, N. C., Franco-Macías, E., Bullido, M. J., Frank-García, A., Froelich, L., Fulton-Howard, B., Galimberti, D., García-Alberca, J. M., García-González, P., Garcia-Madrona, S., Garcia-Ribas, G., Ghidoni, R., Giegling, I., Giorgio, G., Goate, A. M., Goldhardt, O., Gomez-Fonseca, D., González-Pérez, A., Graff, C., Grande, G., Green, E., Grimmer, T., Grünblatt, E., Grunin, M., Gudnason, V., Guetta-Baranes, T., Haapasalo, A., Hadjigeorgiou, G., Haines, J. L., Hamilton-Nelson, K. L., Hampel, H., Hanon, O., Hardy, J., Hartmann, A. M., Hausner, L., Harwood, J., Heilmann-Heimbach, S., Helisalmi, S., Heneka, M. T., Hernández, I., Herrmann, M. J., Hoffmann, P., Holmes, C., Holstege, H., Vilas, R. H., Hulsman, M., Humphrey, J., Biessels, G. J., Jian, X., Johansson, C., Jun, G. R., Kastumata, Y., Kauwe, J., Kehoe, P. G., Kilander, L., Ståhlbom, A. K., Kivipelto, M., Koivisto, A., Kornhuber, J., Kosmidis, M. H., Kukull, W. A., Kuksa, P. P., Kunkle, B. W., Kuzma, A. B., Lage, C., Laukka, E. J., Launer, L., Lauria, A., Lee, C. -Y., Lehtisalo, J., Lerch, O., Lleó, A., Longstreth, W., Lopez, O., de Munain, A. L., Love, S., Löwemark, M., Luckcuck, L., Lunetta, K. L., Ma, Y., Macías, J., Macleod, C. A., Maier, W., Mangialasche, F., Spallazzi, M., Marquié, M., Marshall, R., Martin, E. R., Montes, A. M., Rodríguez, C. M., Masullo, C., Mayeux, R., Mead, S., Mecocci, P., Medina, M., Meggy, A., Mehrabian, S., Mendoza, S., Menéndez-González, M., Mir, P., Moebus, S., Mol, M., Molina-Porcel, L., Montrreal, L., Morelli, L., Moreno, F., Morgan, K., Mosley, T., Nöthen, M. M., Muchnik, C., Mukherjee, S., Nacmias, B., Ngandu, T., Nicolas, G., Nordestgaard, B. G., Olaso, R., Orellana, A., Orsini, M., Ortega, G., Padovani, A., Paolo, C., Papenberg, G., Parnetti, L., Pasquier, F., Pastor, P., Peloso, G., Pérez-Cordón, A., Pérez-Tur, J., Pericard, P., Peters, O., Pijnenburg, Y. A. L., Pineda, J. A., Piñol-Ripoll, G., Pisanu, C., Polak, T., Popp, J., Posthuma, D., Priller, J., Puerta, R., Quenez, O., Quintela, I., Thomassen, J. Q., Rábano, A., Rainero, I., Rajabli, F., Ramakers, I., Real, L. M., Reinders, M. J. T., Reitz, C., Reyes-Dumeyer, D., Ridge, P., Riedel-Heller, S., Riederer, P., Roberto, N., Rodriguez-Rodriguez, E., Rongve, A., Allende, I. R., Rosende-Roca, M., Royo, J. L., Rubino, E., Rujescu, D., Sáez, M. E., Sakka, P., Saltvedt, I., Sanabria, Á., Sánchez-Arjona, M. B., Sanchez-Garcia, F., Juan, P. S., Sánchez-Valle, R., Sando, S. B., Sarnowski, C., Satizabal, C. L., Scamosci, M., Scarmeas, N., Scarpini, E., Scheltens, P., Scherbaum, N., Scherer, M., Schmid, M., Schneider, A., Schott, J. M., Selbæk, G., Seripa, D., Serrano, M., Sha, J., Shadrin, A. A., Skrobot, O., Slifer, S., Snijders, G. J. L., Soininen, H., Solfrizzi, V., Solomon, A., Song, Y. E., Sorbi, S., Sotolongo-Grau, O., Spalletta, G., Spottke, A., Squassina, A., Stordal, E., Tartan, J. P., Tárraga, L., Tesí, N., Thalamuthu, A., Thomas, T., Tosto, G., Traykov, L., Tremolizzo, L., Tybjærg-Hansen, A., Uitterlinden, A., Ullgren, A., Ulstein, I., Valero, S., Valladares, O., Broeckhoven, C. V., Vance, J., Vardarajan, B. N., van der Lugt, A., Dongen, J. V., van Rooij, J., van Swieten, J., Vandenberghe, R., Verhey, F., Vidal, J. -S., Vogelgsang, J., Vyhnalek, M., Wagner, M., Wallon, D., Wang, L. -S., Wang, R., Weinhold, L., Wiltfang, J., Windle, G., Woods, B., Yannakoulia, M., Zare, H., Zhao, Y., Zhang, X., Zhu, C., Zulaica, M., Laczo, J., Matoska, V., Serpente, M., Assogna, F., Piras, F., Ciullo, V., Shofany, J., Ferrarese, C., Andreoni, S., Sala, G., Zoia, C. P., Zompo, M. D., Benussi, A., Bastiani, P., Takalo, M., Natunen, T., Laatikainen, T., Tuomilehto, J., Antikainen, R., Strandberg, T., Lindström, J., Peltonen, M., Abraham, R., Al-Chalabi, A., Bass, N. J., Brayne, C., Brown, K. S., Collinge, J., Craig, D., Deloukas, P., Fox, N., Gerrish, A., Gill, M., Gwilliam, R., Harold, D., Hollingworth, P., Johnston, J. A., Jones, L., Lawlor, B., Livingston, G., Lovestone, S., Lupton, M., Lynch, A., Mann, D., Mcguinness, B., Mcquillin, A., O’Donovan, M. C., Owen, M. J., Passmore, P., Powell, J. F., Proitsi, P., Rossor, M., Shaw, C. E., Smith, A. D., Gurling, H., Todd, S., Mummery, C., Ryan, N., Lacidogna, G., Adarmes-Gómez, A., Mauleón, A., Pancho, A., Gailhajenet, A., Lafuente, A., Macias-García, D., Martín, E., Pelejà, E., Carrillo, F., Merlín, I. S., Garrote-Espina, L., Vargas, L., Carrion-Claro, M., Marín, M., Labrador, M., Buendia, M., Alonso, M. D., Guitart, M., Moreno, M., Ibarria, M., Periñán, M., Aguilera, N., Gómez-Garre, P., Cañabate, P., Escuela, R., Pineda-Sánchez, R., Vigo-Ortega, R., Jesús, S., Preckler, S., Rodrigo-Herrero, S., Diego, S., Vacca, A., Roveta, F., Salvadori, N., Chipi, E., Boecker, H., Laske, C., Perneczky, R., Anastasiou, C., Janowitz, D., Malik, R., Anastasiou, A., Parveen, K., López-García, S., Antonell, A., Mihova, K. Y., Belezhanska, D., Weber, H., Kochen, S., Solis, P., Medel, N., Lisso, J., Sevillano, Z., Politis, D. G., Cores, V., Cuesta, C., Ortiz, C., Bacha, J. I., Rios, M., Saenz, A., Abalos, M. S., Kohler, E., Palacio, D. L., Etchepareborda, I., Kohler, M., Novack, G., Prestia, F. A., Galeano, P., Castaño, E. M., Germani, S., Toso, C. R., Rojo, M., Ingino, C., Mangone, C., Rubinsztein, D. C., Teipel, S., Fievet, N., Deramerourt, V., Forsell, C., Thonberg, H., Bjerke, M., Roeck, E. D., Martínez-Larrad, M. T., Olivar, N., Cano, A., Macias, J., Maroñas, O., Nuñez-Llaves, R., Olivé, C., Adarmes-Gómez, A. D., Amer-Ferrer, G., Antequera, M., Burguera, J. A., Casajeros, M. J., Martinez de Pancorbo, M., Hevilla, S., Espinosa, M. A. L., Legaz, A., Manzanares, S., Marín-Muñoz, J., Marín, T., Martínez, B., Martínez, V., Martínez-Lage Álvarez, P., Iriarte, M. M., Periñán-Tocino, M. T., Real de Asúa, D., Rodrigo, S., Sastre, I., Vicente, M. P., Vivancos, L., Epelbaum, J., Hannequin, D., Campion, D., Deramecourt, V., Tzourio, C., Brice, A., Dubois, B., Williams, A., Thomas, C., Davies, C., Nash, W., Dowzell, K., Morales, A. C., Bernardo-Harrington, M., Turton, J., Lord, J., Brown, K., Vardy, E., Fisher, E., Warren, J. D., Ryan, N. S., Guerreiro, R., Uphill, J., Bass, N., Heun, R., Kölsch, H., Schürmann, B., Lacour, A., Herold, C., Powell, J., Patel, Y., Hodges, A., Becker, T., Warden, D., Wilcock, G., Clarke, R., Ben-Shlomo, Y., Hooper, N. M., Pickering-Brown, S., Sussams, R., Warner, N., Bayer, A., Heuser, I., Drichel, D., Klopp, N., Mayhaus, M., Riemenschneider, M., Pinchler, S., Feulner, T., Gu, W., van den Bussche, H., Hüll, M., Frölich, L., Wichmann, H. -E., Jöckel, K. -H., O’Donovan, M., Owen, M., Bahrami, S., Bosnes, I., Selnes, P., Bergh, S., Palotie, A., Daly, M., Jacob, H., Matakidou, A., Runz, H., John, S., Plenge, R., Mccarthy, M., Hunkapiller, J., Ehm, M., Waterworth, D., Fox, C., Malarstig, A., Klinger, K., Call, K., Behrens, T., Loerch, P., Mäkelä, T., Kaprio, J., Virolainen, P., Pulkki, K., Kilpi, T., Perola, M., Partanen, J., Pitkäranta, A., Kaarteenaho, R., Vainio, S., Turpeinen, M., Serpi, R., Laitinen, T., Mäkelä, J., Kosma, V. -M., Kujala, U., Tuovila, O., Hendolin, M., Pakkanen, R., Waring, J., Riley-Gillis, B., Liu, J., Biswas, S., Diogo, D., Marshall, C., Hu, X., Gossel, M., Graham, R., Cummings, B., Ripatti, S., Schleutker, J., Arvas, M., Carpén, O., Hinttala, R., Kettunen, J., Mannermaa, A., Laukkanen, J., Julkunen, V., Remes, A., Kälviäinen, R., Peltola, J., Tienari, P., Rinne, J., Ziemann, A., Esmaeeli, S., Smaoui, N., Lehtonen, A., Eaton, S., Lahdenperä, S., van Adelsberg, J., Michon, J., Kerchner, G., Bowers, N., Teng, E., Eicher, J., Mehta, V., Gormley, P., Linden, K., Whelan, C., Xu, F., Pulford, D., Färkkilä, M., Pikkarainen, S., Jussila, A., Blomster, T., Kiviniemi, M., Voutilainen, M., Georgantas, B., Heap, G., Rahimov, F., Usiskin, K., Lu, T., Oh, D., Kalpala, K., Miller, M., Mccarthy, L., Eklund, K., Palomäki, A., Isomäki, P., Pirilä, L., Kaipiainen-Seppänen, O., Huhtakangas, J., Lertratanakul, A., Hochfeld, M., Bing, N., Gordillo, J. E., Mars, N., Pelkonen, M., Kauppi, P., Kankaanranta, H., Harju, T., Close, D., Greenberg, S., Chen, H., Betts, J., Ghosh, S., Salomaa, V., Niiranen, T., Juonala, M., Metsärinne, K., Kähönen, M., Junttila, J., Laakso, M., Pihlajamäki, J., Sinisalo, J., Taskinen, M. -R., Tuomi, T., Challis, B., Peterson, A., Chu, A., Parkkinen, J., Muslin, A., Joensuu, H., Meretoja, T., Aaltonen, L., Mattson, J., Auranen, A., Karihtala, P., Kauppila, S., Auvinen, P., Elenius, K., Popovic, R., Schutzman, J., Loboda, A., Chhibber, A., Lehtonen, H., Mcdonough, S., Crohns, M., Kulkarni, D., Kaarniranta, K., Turunen, J. A., Ollila, T., Seitsonen, S., Uusitalo, H., Aaltonen, V., Uusitalo-Järvinen, H., Luodonpää, M., Hautala, N., Loomis, S., Strauss, E., Podgornaia, A., Hoffman, J., Tasanen, K., Huilaja, L., Hannula-Jouppi, K., Salmi, T., Peltonen, S., Koulu, L., Harvima, I., Wu, Y., Choy, D., Pussinen, P., Salminen, A., Salo, T., Rice, D., Nieminen, P., Palotie, U., Siponen, M., Suominen, L., Mäntylä, P., Gursoy, U., Anttonen, V., Sipilä, K., Davis, J. W., Quarless, D., Petrovski, S., Wigmore, E., Chen, C. -Y., Bronson, P., Tsai, E., Huang, Y., Maranville, J., Shaikho, E., Mohammed, E., Wadhawan, S., Kvikstad, E., Caliskan, M., Chang, D., Bhangale, T., Pendergrass, S., Holzinger, E., Chen, X., Hedman, Å., King, K. S., Wang, C., Xu, E., Auge, F., Chatelain, C., Rajpal, D., Liu, D., Xia, T. -H., Brauer, M., Kurki, M., Karjalainen, J., Havulinna, A., Jalanko, A., Palta, P., della Briotta Parolo, P., Zhou, W., Lemmelä, S., Rivas, M., Harju, J., Lehisto, A., Ganna, A., Llorens, V., Laivuori, H., Rüeger, S., Niemi, M. E., Tukiainen, T., Reeve, M. P., Heyne, H., Palin, K., Garcia-Tabuenca, J., Siirtola, H., Kiiskinen, T., Lee, J., Tsuo, K., Elliott, A., Kristiansson, K., Hyvärinen, K., Ritari, J., Koskinen, M., Pylkäs, K., Kalaoja, M., Karjalainen, M., Mantere, T., Kangasniemi, E., Heikkinen, S., Laakkonen, E., Sipeky, C., Heron, S., Karlsson, A., Jambulingam, D., Rathinakannan, V. S., Kajanne, R., Aavikko, M., Jiménez, M. G., della Briotta Parola, P., Kanai, M., Kaunisto, M., Kilpeläinen, E., Sipilä, T. P., Brein, G., Awaisa, G., Shcherban, A., Donner, K., Loukola, A., Laiho, P., Sistonen, T., Kaiharju, E., Laukkanen, M., Järvensivu, E., Lähteenmäki, S., Männikkö, L., Wong, R., Mattsson, H., Hiekkalinna, T., Paajanen, T., Pärn, K., Gracia-Tabuenca, J., Abner, E., Adams, P. M., Aguirre, A., Albert, M. S., Albin, R. L., Allen, M., Alvarez, L., Apostolova, L. G., Arnold, S. E., Asthana, S., Atwood, C. S., Ayres, G., Baldwin, C. T., Barber, R. C., Barnes, L. L., Beach, T. G., Becker, J. T., Beecham, G. W., Beekly, D., Benitez, B. A., Bennett, D., Bertelson, J., Margaret, F. E., Bird, T. D., Blacker, D., Boeve, B. F., Bowen, J. D., Boxer, A., Brewer, J., Burke, J. R., Burns, J. M., Buxbaum, J. D., Cairns, N. J., Cao, C., Carlson, C. S., Carlsson, C. M., Carney, R. M., Carrasquillo, M. M., Chasse, S., Chesselet, M. -F., Chesi, A., Chin, N. A., Chui, H. C., Craft, S., Crane, P. K., Cribbs, D. H., Crocco, E. A., Cruchaga, C., Cullum, M., Darby, E., Davis, B., De Jager, P. L., Decarli, C., Detoledo, J., Dick, M., Dickson, D. W., Dombroski, B. A., Doody, R. S., Duara, R., Ertekin-Taner, N., Evans, D. A., Fairchild, T. J., Fallon, K. B., Farlow, M. R., Farrell, J. J., Fernandez-Hernandez, V., Ferris, S., Frosch, M. P., Galasko, D. R., Gamboa, A., Gearing, M., Geschwind, D. H., Ghetti, B., Gilbert, J. R., Grabowski, T. J., Graff-Radford, N. R., Grant, S. F. A., Green, R. C., Growdon, J. H., Hakonarson, H., Hall, J., Hamilton, R. L., Harari, O., Harrell, L. E., Haut, J., Head, E., Henderson, V. W., Hernandez, M., Hohman, T., Honig, L. S., Huebinger, R. M., Huentelman, M. J., Hulette, C. M., Hyman, B. T., Hynan, L. S., Ibanez, L., Jarvik, G. P., Jayadev, S., Jin, L. -W., Johnson, K., Johnson, L., Kamboh, M. I., Karydas, A. M., Katz, M. J., Kaye, J. A., Keene, C. D., Khaleeq, A., Kim, R., Knebl, J., Kowall, N. W., Kramer, J. H., Laferla, F. M., Lah, J. J., Larson, E. B., Lee, E. B., Lerner, A., Leung, Y. Y., Leverenz, J. B., Levey, A. I., Li, M., Lieberman, A. P., Lipton, R. B., Logue, M., Lyketsos, C. G., Malamon, J., Mains, D., Marson, D. C., Martiniuk, F., Mash, D. C., Masliah, E., Massman, P., Masurkar, A., Mccormick, W. C., Mccurry, S. M., Mcdavid, A. N., Mckee, A. C., Mesulam, M., Mez, J., Miller, B. L., Miller, C. A., Miller, J. W., Montine, T. J., Monuki, E. S., Morris, J. C., Myers, A. J., Nguyen, T., O’Bryant, S., Olichney, J. M., Ory, M., Palmer, R., Parisi, J. E., Paulson, H. L., Pavlik, V., Paydarfar, D., Perez, V., Peskind, E., Petersen, R. C., Phillips-Cremins, J. E., Pierce, A., Polk, M., Poon, W. W., Potter, H., Qu, L., Quiceno, M., Quinn, J. F., Raj, A., Raskind, M., Reiman, E. M., Reisberg, B., Reisch, J. S., Ringman, J. M., Roberson, E. D., Rodriguear, M., Rogaeva, E., Rosen, H. J., Rosenberg, R. N., Royall, D. R., Sager, M. A., Sano, M., Saykin, A. J., Schneider, J. A., Schneider, L. S., Seeley, W. W., Small, S., Smith, A. G., Smith, J. P., Sonnen, J. A., Spina, S., George-Hyslop, P. S., Stern, R. A., Stevens, A. B., Strittmatter, S. M., Sultzer, D., Swerdlow, R. H., Tanzi, R. E., Tilson, J. L., Trojanowski, J. Q., Troncoso, J. C., Tsuang, D. W., Van Deerlin, V. M., van Eldik, L. J., Vassar, R., Vinters, H. V., Vonsattel, J. -P., Weintraub, S., Welsh-Bohmer, K. A., Whitehead, P. L., Wijsman, E. M., Wilhelmsen, K. C., Williams, B., Williamson, J., Wilms, H., Wingo, T. S., Wisniewski, T., Woltjer, R. L., Woon, M., Wright, C. B., C. -K., Wu, Younkin, S. G., C. -E., Yu, Yu, L., Zhang, Y., Zhu, X., Adams, H., Akinyemi, R. O., Ali, M., Armstrong, N., Aparicio, H. J., Bahadori, M., Breteler, M., Chasman, D., Chauhan, G., Comic, H., Cox, S., Cupples, A. L., Davies, G., Decarli, C. S., Duperron, M. -G., Dupuis, J., Evans, T., Fan, F., Fitzpatrick, A., Fohner, A. E., Ganguli, M., Geerlings, M., Glatt, S. J., Gonzalez, H. M., Goss, M., Grabe, H., Habes, M., Heckbert, S. R., Hofer, E., Hong, E., Hughes, T., Kautz, T. F., Knol, M., Kremen, W., Lacaze, P., Lahti, J., Grand, Q. L., Litkowski, E., Li, S., Liu, X., Loitfelder, M., Manning, A., Maillard, P., Marioni, R., Mazoyer, B., van Lent, D. M., Mei, H., Mishra, A., Nyquist, P., O’Connell, J., Paus, T., Pausova, Z., Raikkonen-Talvitie, K., Riaz, M., Rich, S., Rotter, J., Romero, J., Roshchupkin, G., Saba, Y., Sargurupremraj, M., Schmidt, H., Schmidt, R., Shulman, J. M., Smith, J., Sekhar, H., Rajula, R., Shin, J., Simino, J., Sliz, E., Teumer, A., Thomas, A., Tin, A., Tucker-Drob, E., Vojinovic, D., Wang, Y., Weinstein, G., Williams, D., Wittfeld, K., Yanek, L., Yang, Y., Farrer, L. A., Psaty, B. M., Ghanbari, M., Raj, T., Sachdev, P., Mather, K., Jessen, F., Ikram, M. A., de Mendonça, A., Hort, J., Tsolaki, M., Pericak-Vance, M. A., Amouyel, P., Williams, J., Frikke-Schmidt, R., Clarimon, J., Deleuze, J. -F., Rossi, G., Seshadri, S., Andreassen, O. A., Ingelsson, M., Hiltunen, M., Sleegers, K., Schellenberg, G. D., van Duijn, C. M., Sims, R., van der Flier, W. M., Ruiz, A., Ramirez, A., Lambert J., -C, Jan, Laczo, Vaclav, Matoska, Maria, Serpente, Francesca, Assogna, Fabrizio, Piras, Federica, Piras, Valentina, Ciullo, Jacob, Shofany, Carlo, Ferrarese, Simona, Andreoni, Gessica, Sala, Chiara Paola Zoia, Maria Del Zompo, Benussi, Alberto, Patrizia, Bastiani, Mari, Takalo, Teemu, Natunen, Tiina, Laatikainen, Jaakko, Tuomilehto, Riitta, Antikainen, Timo, Strandberg, Jaana, Lindström, Markku, Peltonen, Richard, Abraham, Ammar, Al-Chalabi, Nicholas, J Bass, Carol, Brayne, Kristelle, S Brown, John, Collinge, David, Craig, Pangiotis, Deloukas, Nick, Fox, Amy, Gerrish, Michael, Gill, Rhian, Gwilliam, Denise, Harold, Paul, Hollingworth, Jarret, A Johnston, Lesley, Jones, Brian, Lawlor, Gill, Livingston, Simon, Lovestone, Michelle, Lupton, Aoibhinn, Lynch, David, Mann, Bernadette, Mcguinness, Andrew, Mcquillin, Michael, C O'Donovan, Michael, J Owen, Peter, Passmore, John, F Powell, Petra, Proitsi, Martin, Rossor, Christopher, E Shaw, A David Smith, Hugh, Gurling, Stephen, Todd, Catherine, Mummery, Nathalie, Ryan, Giordano, Lacidogna, Adarmes-Gómez, Ad, Ana, Mauleón, Ana, Pancho, Anna, Gailhajenet, Asunción, Lafuente, Macias-García, D, Elvira, Martín, Esther, Pelejà, Carrillo, F, Isabel Sastre Merlín, Garrote-Espina, L, Liliana, Vargas, Carrion-Claro, M, Marín, M, Labrador, Ma, Mar, Buendia, María Dolores Alonso, Marina, Guitart, Mariona, Moreno, Marta, Ibarria, Periñán, Mt, Nuria, Aguilera, Gómez-Garre, P, Pilar, Cañabate, Escuela, R, Pineda-Sánchez, R, Vigo-Ortega, R, Jesús, S, Silvia, Preckler, Silvia, Rodrigo-Herrero, Susana, Diego, Alessandro, Vacca, Fausto, Roveta, Nicola, Salvadori, Elena, Chipi, Henning, Boecker, Christoph, Laske, Robert, Perneczky, Costas, Anastasiou, Daniel, Janowitz, Rainer, Malik, Anna, Anastasiou, Kayenat, Parveen, Carmen, Lage, Sara, López-García, Anna, Antonell, Kalina Yonkova Mihova, Diyana, Belezhanska, Heike, Weber, Silvia, Kochen, Patricia, Solis, Nancy, Medel, Julieta, Lisso, Zulma, Sevillano, Daniel, G Politis, Valeria, Cores, Carolina, Cuesta, Cecilia, Ortiz, Juan Ignacio Bacha, Mario, Rios, Aldo, Saenz, Mariana Sanchez Abalos, Eduardo, Kohler, Dana Lis Palacio, Ignacio, Etchepareborda, Matias, Kohler, Gisela, Novack, Federico Ariel Prestia, Pablo, Galeano, Eduardo, M Castaño, Sandra, Germani, Carlos Reyes Toso, Matias, Rojo, Carlos, Ingino, Carlos, Mangone, David, C Rubinsztein, Stefan, Teipel, Nathalie, Fievet, Vincent, Deramerourt, Charlotte, Forsell, Håkan, Thonberg, Maria, Bjerke, Ellen De Roeck, María Teresa Martínez-Larrad, Natividad, Olivar, Amanda, Cano, Juan, Macias, Olalla, Maroñas, Raúl, Nuñez-Llaves, Clàudia, Olivé, Ester, Pelejá, Astrid, D Adarmes-Gómez, Guillermo, Amer-Ferrer, Martirio, Antequera, Juan Andrés Burguera, Fátima, Carrillo, Mario, Carrión-Claro, María José Casajeros, Marian Martinez de Pancorbo, Rocío, Escuela, Lorena, Garrote-Espina, Pilar, Gómez-Garre, Saray, Hevilla, Silvia, Jesús, Miguel Angel Labrador Espinosa, Agustina, Legaz, Daniel, Macias-García, Salvadora, Manzanares, Marta, Marín, Juan, Marín-Muñoz, Tamara, Marín, Begoña, Martínez, Victoriana, Martínez, Pablo Martínez-Lage Álvarez, Maite Mendioroz Iriarte, María Teresa Periñán-Tocino, Rocío, Pineda-Sánchez, Diego Real de Asúa, Silvia, Rodrigo, Isabel, Sastre, Maria Pilar Vicente, Rosario, Vigo-Ortega, Liliana, Vivancos, Jacques, Epelbaum, Didier, Hannequin, Dominique, Campion, Vincent, Deramecourt, Christophe, Tzourio, Alexis, Brice, Bruno, Dubois, Amy, Williams, Charlene, Thomas, Chloe, Davies, William, Nash, Kimberley, Dowzell, Atahualpa Castillo Morales, Mateus, Bernardo-Harrington, James, Turton, Jenny, Lord, Kristelle, Brown, Emma, Vardy, Elizabeth, Fisher, Jason, D Warren, Natalie, S Ryan, Rita, Guerreiro, James, Uphill, Nick, Bass, Reinhard, Heun, Heike, Kölsch, Britta, Schürmann, André, Lacour, Christine, Herold, Janet, A Johnston, John, Powell, Yogen, Patel, Angela, Hodges, Tim, Becker, Donald, Warden, Gordon, Wilcock, Robert, Clarke, Panagiotis, Deloukas, Yoav, Ben-Shlomo, Nigel, M Hooper, Stuart, Pickering-Brown, Rebecca, Sussams, Nick, Warner, Anthony, Bayer, Isabella, Heuser, Dmitriy, Drichel, Norman, Klopp, Manuel, Mayhaus, Matthias, Riemenschneider, Sabrina, Pinchler, Thomas, Feulner, Wei, Gu, Hendrik van den Bussche, Michael, Hüll, Lutz, Frölich, H-Erich, Wichmann, Karl-Heinz, Jöckel, Michael, O'Donovan, Michael, Owen, Shahram, Bahrami, Ingunn, Bosnes, Per, Selnes, Sverre, Bergh, Aarno, Palotie, Mark, Daly, Howard, Jacob, Athena, Matakidou, Heiko, Runz, Sally, John, Robert, Plenge, Mark, Mccarthy, Julie, Hunkapiller, Meg, Ehm, Dawn, Waterworth, Caroline, Fox, Anders, Malarstig, Kathy, Klinger, Kathy, Call, Tim, Behrens, Patrick, Loerch, Tomi, Mäkelä, Jaakko, Kaprio, Petri, Virolainen, Kari, Pulkki, Terhi, Kilpi, Markus, Perola, Jukka, Partanen, Anne, Pitkäranta, Riitta, Kaarteenaho, Seppo, Vainio, Miia, Turpeinen, Raisa, Serpi, Tarja, Laitinen, Johanna, Mäkelä, Veli-Matti, Kosma, Urho, Kujala, Outi, Tuovila, Minna, Hendolin, Raimo, Pakkanen, Jeff, Waring, Bridget, Riley-Gillis, Jimmy, Liu, Shameek, Biswas, Dorothee, Diogo, Catherine, Marshall, Xinli, Hu, Matthias, Gossel, Robert, Graham, Beryl, Cummings, Samuli, Ripatti, Johanna, Schleutker, Mikko, Arvas, Olli, Carpén, Reetta, Hinttala, Johannes, Kettunen, Arto, Mannermaa, Jari, Laukkanen, Valtteri, Julkunen, Anne, Remes, Reetta, Kälviäinen, Jukka, Peltola, Pentti, Tienari, Juha, Rinne, Adam, Ziemann, Jeffrey, Waring, Sahar, Esmaeeli, Nizar, Smaoui, Anne, Lehtonen, Susan, Eaton, Sanni, Lahdenperä, Janet van Adelsberg, John, Michon, Geoff, Kerchner, Natalie, Bowers, Edmond, Teng, John, Eicher, Vinay, Mehta, Padhraig, Gormley, Kari, Linden, Christopher, Whelan, Fanli, Xu, David, Pulford, Martti, Färkkilä, Sampsa, Pikkarainen, Airi, Jussila, Timo, Blomster, Mikko, Kiviniemi, Markku, Voutilainen, Bob, Georgantas, Graham, Heap, Fedik, Rahimov, Keith, Usiskin, Tim, Lu, Danny, Oh, Kirsi, Kalpala, Melissa, Miller, Linda, Mccarthy, Kari, Eklund, Antti, Palomäki, Pia, Isomäki, Laura, Pirilä, Oili, Kaipiainen-Seppänen, Johanna, Huhtakangas, Apinya, Lertratanakul, Marla, Hochfeld, Nan, Bing, Jorge Esparza Gordillo, Nina, Mars, Margit, Pelkonen, Paula, Kauppi, Hannu, Kankaanranta, Terttu, Harju, David, Close, Steven, Greenberg, Hubert, Chen, Betts, Jo, Soumitra, Ghosh, Veikko, Salomaa, Teemu, Niiranen, Markus, Juonala, Kaj, Metsärinne, Mika, Kähönen, Juhani, Junttila, Markku, Laakso, Jussi, Pihlajamäki, Juha, Sinisalo, Marja-Riitta, Taskinen, Tiinamaija, Tuomi, Ben, Challis, Andrew, Peterson, Audrey, Chu, Jaakko, Parkkinen, Anthony, Muslin, Heikki, Joensuu, Tuomo, Meretoja, Lauri, Aaltonen, Johanna, Mattson, Annika, Auranen, Peeter, Karihtala, Saila, Kauppila, Päivi, Auvinen, Klaus, Elenius, Relja, Popovic, Jennifer, Schutzman, Andrey, Loboda, Aparna, Chhibber, Heli, Lehtonen, Stefan, Mcdonough, Marika, Crohns, Diptee, Kulkarni, Kai, Kaarniranta, Joni, A Turunen, Terhi, Ollila, Sanna, Seitsonen, Hannu, Uusitalo, Vesa, Aaltonen, Hannele, Uusitalo-Järvinen, Marja, Luodonpää, Nina, Hautala, Stephanie, Loomis, Erich, Strauss, Hao, Chen, Anna, Podgornaia, Joshua, Hoffman, Kaisa, Tasanen, Laura, Huilaja, Katariina, Hannula-Jouppi, Teea, Salmi, Sirkku, Peltonen, Leena, Koulu, Ilkka, Harvima, Ying, Wu, David, Choy, Pirkko, Pussinen, Aino, Salminen, Tuula, Salo, David, Rice, Pekka, Nieminen, Ulla, Palotie, Maria, Siponen, Liisa, Suominen, Päivi, Mäntylä, Ulvi, Gursoy, Vuokko, Anttonen, Kirsi, Sipilä, Justin Wade Davis, Danjuma, Quarless, Slavé, Petrovski, Eleonor, Wigmore, Chia-Yen, Chen, Paola, Bronson, Ellen, Tsai, Yunfeng, Huang, Joseph, Maranville, Elmutaz, Shaikho, Elhaj, Mohammed, Samir, Wadhawan, Erika, Kvikstad, Minal, Caliskan, Diana, Chang, Tushar, Bhangale, Sarah, Pendergrass, Emily, Holzinger, Xing, Chen, Åsa, Hedman, Karen, S King, Clarence, Wang, Ethan, Xu, Franck, Auge, Clement, Chatelain, Deepak, Rajpal, Dongyu, Liu, Katherine, Call, Tai-He, Xia, Matt, Brauer, Mitja, Kurki, Juha, Karjalainen, Aki, Havulinna, Anu, Jalanko, Priit, Palta, Pietro Della Briotta Parolo, Wei, Zhou, Susanna, Lemmelä, Manuel, Rivas, Jarmo, Harju, Arto, Lehisto, Andrea, Ganna, Vincent, Llorens, Hannele, Laivuori, Sina, Rüeger, Mari, E Niemi, Taru, Tukiainen, Mary Pat Reeve, Henrike, Heyne, Kimmo, Palin, Javier, Garcia-Tabuenca, Harri, Siirtola, Tuomo, Kiiskinen, Jiwoo, Lee, Kristin, Tsuo, Amanda, Elliott, Kati, Kristiansson, Kati, Hyvärinen, Jarmo, Ritari, Miika, Koskinen, Katri, Pylkäs, Marita, Kalaoja, Minna, Karjalainen, Tuomo, Mantere, Eeva, Kangasniemi, Sami, Heikkinen, Eija, Laakkonen, Csilla, Sipeky, Samuel, Heron, Antti, Karlsson, Dhanaprakash, Jambulingam, Venkat Subramaniam Rathinakannan, Risto, Kajanne, Mervi, Aavikko, Manuel González Jiménez, Pietro Della Briotta Parola, Arto, Lehistö, Masahiro, Kanai, Mari, Kaunisto, Elina, Kilpeläinen, Timo, P Sipilä, Georg, Brein, Ghazal, Awaisa, Anastasia, Shcherban, Kati, Donner, Anu, Loukola, Päivi, Laiho, Tuuli, Sistonen, Essi, Kaiharju, Markku, Laukkanen, Elina, Järvensivu, Sini, Lähteenmäki, Lotta, Männikkö, Regis, Wong, Hannele, Mattsson, Tero, Hiekkalinna, Teemu, Paajanen, Kalle, Pärn, Javier, Gracia-Tabuenca, Erin, Abner, Perrie, M Adams, Alyssa, Aguirre, Marilyn, S Albert, Roger, L Albin, Mariet, Allen, Lisa, Alvarez, Liana, G Apostolova, Steven, E Arnold, Sanjay, Asthana, Craig, S Atwood, Gayle, Ayres, Clinton, T Baldwin, Robert, C Barber, Lisa, L Barnes, Sandra, Barral, Thomas, G Beach, James, T Becker, Gary, W Beecham, Duane, Beekly, Jennifer, E Below, Penelope, Benchek, Bruno, A Benitez, David, Bennett, John, Bertelson, Flanagan, E Margaret, Thomas, D Bird, Deborah, Blacker, Bradley, F Boeve, James, D Bowen, Adam, Boxer, James, Brewer, James, R Burke, Jeffrey, M Burns, Will, S Bush, Joseph, D Buxbaum, Nigel, J Cairns, Chuanhai, Cao, Christopher, S Carlson, Cynthia, M Carlsson, Regina, M Carney, Minerva, M Carrasquillo, Scott, Chasse, Marie-Francoise, Chesselet, Alessandra, Chesi, Nathaniel, A Chin, Helena, C Chui, Jaeyoon, Chung, Suzanne, Craft, Paul, K Crane, David, H Cribbs, Elizabeth, A Crocco, Carlos, Cruchaga, Michael, L Cuccaro, Munro, Cullum, Eveleen, Darby, Barbara, Davis, Philip, L De Jager, Charles, Decarli, John, Detoledo, Malcolm, Dick, Dennis, W Dickson, Beth, A Dombroski, Rachelle, S Doody, Ranjan, Duara, Nilüfer, Ertekin-Taner, Denis, A Evans, Thomas, J Fairchild, Kenneth, B Fallon, Martin, R Farlow, John, J Farrell, Victoria, Fernandez-Hernandez, Steven, Ferris, Matthew, P Frosch, Brian, Fulton-Howard, Douglas, R Galasko, Adriana, Gamboa, Marla, Gearing, Daniel, H Geschwind, Bernardino, Ghetti, John, R Gilbert, Thomas, J Grabowski, Neill, R Graff-Radford, Struan F, A Grant, Robert, C Green, John, H Growdon, Jonathan, L Haines, Hakon, Hakonarson, James, Hall, Ronald, L Hamilton, Oscar, Harari, Lindy, E Harrell, Jacob, Haut, Elizabeth, Head, Victor, W Henderson, Michelle, Hernandez, Timothy, Hohman, Lawrence, S Honig, Ryan, M Huebinger, Matthew, J Huentelman, Christine, M Hulette, Bradley, T Hyman, Linda, S Hynan, Laura, Ibanez, Gail, P Jarvik, Suman, Jayadev, Lee-Way, Jin, Kim, Johnson, Leigh, Johnson, M Ilyas Kamboh, Anna, M Karydas, Mindy, J Katz, Jeffrey, A Kaye, C Dirk Keene, Aisha, Khaleeq, Ronald, Kim, Janice, Knebl, Neil, W Kowall, Joel, H Kramer, Pavel, P Kuksa, Frank, M LaFerla, James, J Lah, Eric, B Larson, Chien-Yueh, Lee, Edward, B Lee, Alan, Lerner, Yuk Yee Leung, James, B Leverenz, Allan, I Levey, Mingyao, Li, Andrew, P Lieberman, Richard, B Lipton, Mark, Logue, Constantine, G Lyketsos, John, Malamon, Douglas, Mains, Daniel, C Marson, Frank, Martiniuk, Deborah, C Mash, Eliezer, Masliah, Paul, Massman, Arjun, Masurkar, Wayne, C McCormick, Susan, M McCurry, Andrew, N McDavid, Ann, C McKee, Marsel, Mesulam, Jesse, Mez, Bruce, L Miller, Carol, A Miller, Joshua, W Miller, Thomas, J Montine, Edwin, S Monuki, John, C Morris, Amanda, J Myers, Trung, Nguyen, Sid, O'Bryant, John, M Olichney, Marcia, Ory, Raymond, Palmer, Joseph, E Parisi, Henry, L Paulson, Valory, Pavlik, David, Paydarfar, Victoria, Perez, Elaine, Peskind, Ronald, C Petersen, Jennifer, E Phillips-Cremins, Aimee, Pierce, Marsha, Polk, Wayne, W Poon, Huntington, Potter, Liming, Qu, Mary, Quiceno, Joseph, F Quinn, Ashok, Raj, Murray, Raskind, Eric, M Reiman, Barry, Reisberg, Joan, S Reisch, John, M Ringman, Erik, D Roberson, Monica, Rodriguear, Ekaterina, Rogaeva, Howard, J Rosen, Roger, N Rosenberg, Donald, R Royall, Mark, A Sager, Mary, Sano, Andrew, J Saykin, Julie, A Schneider, Lon, S Schneider, William, W Seeley, Susan, H Slifer, Scott, Small, Amanda, G Smith, Janet, P Smith, Yeunjoo, E Song, Joshua, A Sonnen, Salvatore, Spina, Peter St George-Hyslop, Robert, A Stern, Alan, B Stevens, Stephen, M Strittmatter, David, Sultzer, Russell, H Swerdlow, Rudolph, E Tanzi, Jeffrey, L Tilson, John, Q Trojanowski, Juan, C Troncoso, Debby, W Tsuang, Otto, Valladares, Vivianna, M Van Deerlin, Linda, J van Eldik, Robert, Vassar, Harry, V Vinters, Jean-Paul, Vonsattel, Sandra, Weintraub, Kathleen, A Welsh-Bohmer, Patrice, L Whitehead, Ellen, M Wijsman, Kirk, C Wilhelmsen, Benjamin, Williams, Jennifer, Williamson, Henrik, Wilms, Thomas, S Wingo, Thomas, Wisniewski, Randall, L Woltjer, Martin, Woon, Clinton, B Wright, Chuang-Kuo, Wu, Steven, G Younkin, Chang-En, Yu, Lei, Yu, Yuanchao, Zhang, Zhao, Yi, Xiongwei, Zhu, Hieab, Adams, Rufus, O Akinyemi, Muhammad, Ali, Nicola, Armstrong, Hugo, J Aparicio, Maryam, Bahadori, Monique, Breteler, Daniel, Chasman, Ganesh, Chauhan, Hata, Comic, Simon, Cox, Adrienne, L Cupples, Gail, Davies, Charles, S DeCarli, Marie-Gabrielle, Duperron, Josée, Dupuis, Tavia, Evans, Frank, Fan, Annette, Fitzpatrick, Alison, E Fohner, Mary, Ganguli, Mirjam, Geerlings, Stephen, J Glatt, Hector, M Gonzalez, Monica, Goss, Hans, Grabe, Mohamad, Habes, Susan, R Heckbert, Edith, Hofer, Elliot, Hong, Timothy, Hughes, Tiffany, F Kautz, Maria, Knol, William, Kremen, Paul, Lacaze, Jari, Lahti, Quentin Le Grand, Elizabeth, Litkowski, Shuo, Li, Dan, Liu, Xuan, Liu, Marisa, Loitfelder, Alisa, Manning, Pauline, Maillard, Riccardo, Marioni, Bernard, Mazoyer, Debora Melo van Lent, Hao, Mei, Aniket, Mishra, Paul, Nyquist, Jeffrey, O'Connell, Yash, Patel, Tomas, Paus, Zdenka, Pausova, Katri, Raikkonen-Talvitie, Moeen, Riaz, Stephen, Rich, Jerome, Rotter, Jose, Romero, Gena, Roshchupkin, Yasaman, Saba, Murali, Sargurupremraj, Helena, Schmidt, Reinhold, Schmidt, Joshua, M Shulman, Jennifer, Smith, Hema, Sekhar, Reddy, Rajula, Jean, Shin, Jeannette, Simino, Eeva, Sliz, Alexander, Teumer, Alvin, Thomas, Adrienne, Tin, Elliot, Tucker-Drob, Dina, Vojinovic, Yanbing, Wang, Galit, Weinstein, Dylan, Williams, Katharina, Wittfeld, Lisa, Yanek, Yunju, Yang, Bellenguez, C, Küçükali, F, Jansen, I, Kleineidam, L, Moreno-Grau, S, Amin, N, Naj, A, Campos-Martin, R, Grenier-Boley, B, Andrade, V, Holmans, P, Boland, A, Damotte, V, van der Lee, S, Costa, M, Kuulasmaa, T, Yang, Q, de Rojas, I, Bis, J, Yaqub, A, Prokic, I, Chapuis, J, Ahmad, S, Giedraitis, V, Aarsland, D, Garcia-Gonzalez, P, Abdelnour, C, Alarcón-Martín, E, Alcolea, D, Alegret, M, Alvarez, I, Álvarez, V, Armstrong, N, Tsolaki, A, Antúnez, C, Appollonio, I, Arcaro, M, Archetti, S, Pastor, A, Arosio, B, Athanasiu, L, Bailly, H, Banaj, N, Baquero, M, Barral, S, Beiser, A, Below, J, Benchek, P, Benussi, L, Berr, C, Besse, C, Bessi, V, Binetti, G, Bizarro, A, Blesa, R, Boada, M, Boerwinkle, E, Borroni, B, Boschi, S, Bossù, P, Bråthen, G, Bressler, J, Bresner, C, Brodaty, H, Brookes, K, Brusco, L, Buiza-Rueda, D, Bûrger, K, Burholt, V, Bush, W, Calero, M, Cantwell, L, Chene, G, Chung, J, Cuccaro, M, Carracedo, Á, Cecchetti, R, Cervera-Carles, L, Charbonnier, C, Chen, H, Chillotti, C, Ciccone, S, Claassen, J, Clark, C, Conti, E, Corma-Gómez, A, Costantini, E, Custodero, C, Daian, D, Dalmasso, M, Daniele, A, Dardiotis, E, Dartigues, J, de Deyn, P, de Paiva Lopes, K, de Witte, L, Debette, S, Deckert, J, Del Ser, T, Denning, N, Destefano, A, Dichgans, M, Diehl-Schmid, J, Diez-Fairen, M, Rossi, P, Djurovic, S, Duron, E, Düzel, E, Dufouil, C, Eiriksdottir, G, Engelborghs, S, Escott-Price, V, Espinosa, A, Ewers, M, Faber, K, Fabrizio, T, Nielsen, S, Fardo, D, Farotti, L, Fenoglio, C, Fernández-Fuertes, M, Ferrari, R, Ferreira, C, Ferri, E, Fin, B, Fischer, P, Fladby, T, Fließbach, K, Fongang, B, Fornage, M, Fortea, J, Foroud, T, Fostinelli, S, Fox, N, Franco-Macías, E, Bullido, M, Frank-García, A, Froelich, L, Fulton-Howard, B, Galimberti, D, García-Alberca, J, García-González, P, Garcia-Madrona, S, Garcia-Ribas, G, Ghidoni, R, Giegling, I, Giorgio, G, Goate, A, Goldhardt, O, Gomez-Fonseca, D, González-Pérez, A, Graff, C, Grande, G, Green, E, Grimmer, T, Grünblatt, E, Grunin, M, Gudnason, V, Guetta-Baranes, T, Haapasalo, A, Hadjigeorgiou, G, Haines, J, Hamilton-Nelson, K, Hampel, H, Hanon, O, Hardy, J, Hartmann, A, Hausner, L, Harwood, J, Heilmann-Heimbach, S, Helisalmi, S, Heneka, M, Hernández, I, Herrmann, M, Hoffmann, P, Holmes, C, Holstege, H, Vilas, R, Hulsman, M, Humphrey, J, Biessels, G, Jian, X, Johansson, C, Jun, G, Kastumata, Y, Kauwe, J, Kehoe, P, Kilander, L, Ståhlbom, A, Kivipelto, M, Koivisto, A, Kornhuber, J, Kosmidis, M, Kukull, W, Kuksa, P, Kunkle, B, Kuzma, A, Lage, C, Laukka, E, Launer, L, Lauria, A, Lee, C, Lehtisalo, J, Lerch, O, Lleó, A, Longstreth, W, Lopez, O, de Munain, A, Love, S, Löwemark, M, Luckcuck, L, Lunetta, K, Ma, Y, Macías, J, Macleod, C, Maier, W, Mangialasche, F, Spallazzi, M, Marquié, M, Marshall, R, Martin, E, Montes, A, Rodríguez, C, Masullo, C, Mayeux, R, Mead, S, Mecocci, P, Medina, M, Meggy, A, Mehrabian, S, Mendoza, S, Menéndez-González, M, Mir, P, Moebus, S, Mol, M, Molina-Porcel, L, Montrreal, L, Morelli, L, Moreno, F, Morgan, K, Mosley, T, Nöthen, M, Muchnik, C, Mukherjee, S, Nacmias, B, Ngandu, T, Nicolas, G, Nordestgaard, B, Olaso, R, Orellana, A, Orsini, M, Ortega, G, Padovani, A, Paolo, C, Papenberg, G, Parnetti, L, Pasquier, F, Pastor, P, Peloso, G, Pérez-Cordón, A, Pérez-Tur, J, Pericard, P, Peters, O, Pijnenburg, Y, Pineda, J, Piñol-Ripoll, G, Pisanu, C, Polak, T, Popp, J, Posthuma, D, Priller, J, Puerta, R, Quenez, O, Quintela, I, Thomassen, J, Rábano, A, Rainero, I, Rajabli, F, Ramakers, I, Real, L, Reinders, M, Reitz, C, Reyes-Dumeyer, D, Ridge, P, Riedel-Heller, S, Riederer, P, Roberto, N, Rodriguez-Rodriguez, E, Rongve, A, Allende, I, Rosende-Roca, M, Royo, J, Rubino, E, Rujescu, D, Sáez, M, Sakka, P, Saltvedt, I, Sanabria, Á, Sánchez-Arjona, M, Sanchez-Garcia, F, Juan, P, Sánchez-Valle, R, Sando, S, Sarnowski, C, Satizabal, C, Scamosci, M, Scarmeas, N, Scarpini, E, Scheltens, P, Scherbaum, N, Scherer, M, Schmid, M, Schneider, A, Schott, J, Selbæk, G, Seripa, D, Serrano, M, Sha, J, Shadrin, A, Skrobot, O, Slifer, S, Snijders, G, Soininen, H, Solfrizzi, V, Solomon, A, Song, Y, Sorbi, S, Sotolongo-Grau, O, Spalletta, G, Spottke, A, Squassina, A, Stordal, E, Tartan, J, Tárraga, L, Tesí, N, Thalamuthu, A, Thomas, T, Tosto, G, Traykov, L, Tremolizzo, L, Tybjærg-Hansen, A, Uitterlinden, A, Ullgren, A, Ulstein, I, Valero, S, Valladares, O, Broeckhoven, C, Vance, J, Vardarajan, B, van der Lugt, A, Dongen, J, van Rooij, J, van Swieten, J, Vandenberghe, R, Verhey, F, Vidal, J, Vogelgsang, J, Vyhnalek, M, Wagner, M, Wallon, D, Wang, L, Wang, R, Weinhold, L, Wiltfang, J, Windle, G, Woods, B, Yannakoulia, M, Zare, H, Zhao, Y, Zhang, X, Zhu, C, Zulaica, M, Andreoni, S, Ferrarese, C, Sala, G, Zoia, C, Farrer, L, Psaty, B, Ghanbari, M, Raj, T, Sachdev, P, Mather, K, Jessen, F, Ikram, M, de Mendonça, A, Hort, J, Tsolaki, M, Pericak-Vance, M, Amouyel, P, Williams, J, Frikke-Schmidt, R, Clarimon, J, Deleuze, J, Rossi, G, Seshadri, S, Andreassen, O, Ingelsson, M, Hiltunen, M, Sleegers, K, Schellenberg, G, van Duijn, C, Sims, R, van der Flier, W, Ruiz, A, Ramirez, A, Lambert, J, VU University medical center, Amsterdam Neuroscience - Neurodegeneration, Neurology, Human genetics, Amsterdam Neuroscience - Complex Trait Genetics, Amsterdam Neuroscience - Compulsivity, 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Spec Psychiatrie (9), UAM. Departamento de Biología Molecular, University of Helsinki, Department of Neurosciences, HUS Internal Medicine and Rehabilitation, Timo Strandberg / Principal Investigator, Department of Medicine, Clinicum, HUS Neurocenter, Neurologian yksikkö, Centre of Excellence in Complex Disease Genetics, HUS Abdominal Center, Institut Pasteur, Institut National de la Santé et de la Recherche Médicale (France), European Commission, LabEx DISTALZ, Pérez-Tur, Jordi, University Children’s Hospital Basel (Suiza), INSERM (Francia), Lille Métropole Communauté Urbaine, Government of France (Francia), EADB, GR@ACE, DEGESCO, EADI, GERAD, Demgene, FinnGen, ADGC, CHARGE, Holmans, Peter A. [0000-0003-0870-9412], van der Lee, Sven J. [0000-0003-1606-8643], Costa, Marcos R. [0000-0002-4928-2163], Bis, Joshua C. [0000-0002-3409-1110], Brookes, Keeley J. [0000-0003-2427-2513], Bush, William S. [0000-0002-9729-6519], de Witte, Lot D. [0000-0002-7235-9958], del Ser, Teodoro [0000-0001-9806-7083], Fox, Nick C. [0000-0002-6660-657X], Bullido, María J. [0000-0002-6477-1117], Goate, Alison M. [0000-0002-0576-2472], Herrmann, Martin J. [0000-0001-9970-2122], Jun, Gyungah R. [0000-0002-3230-8697], Kehoe, Patrick G. [0000-0002-7542-1139], Kosmidis, Mary H. [0000-0001-8790-1220], Lunetta, Kathryn L. [0000-0002-9268-810X], MacLeod, Catherine A. [0000-0002-9314-7380], Nöthen, Markus M. [0000-0002-8770-2464], Nordestgaard, Børge G. [0000-0002-1954-7220], Pineda, Juan A. [0000-0002-3751-0296], Real, Luis M. [0000-0003-4932-7429], Reinders, Marcel J. T. [0000-0002-1148-1562], Satizabal, Claudia L. [0000-0002-1115-4430], Schott, Jonathan M. [0000-0003-2059-024X], Shadrin, Alexey A. [0000-0002-7467-250X], Farrer, Lindsay A. [0000-0001-5533-4225], Psaty, Bruce M. [0000-0002-7278-2190], Ikram, M. Arfan [0000-0003-0372-8585], Pericak-Vance, Margaret A. [0000-0001-7283-8804], Andreassen, Ole A. [0000-0002-4461-3568], van Duijn, Cornelia M. [0000-0002-2374-9204], van der Flier, Wiesje M. [0000-0001-8766-6224], and Molecular Neuroscience and Ageing Research (MOLAR)
- Subjects
tau Proteins/genetics ,Alzheimer`s disease Donders Center for Medical Neuroscience [Radboudumc 1] ,Neurologi ,MED/03 - GENETICA MEDICA ,45/43 ,Medizin ,Stress-related disorders Donders Center for Medical Neuroscience [Radboudumc 13] ,genetics [Alzheimer Disease] ,Genome-Wide Association Study ,Humans ,tau Proteins ,Alzheimer Disease ,Cognitive Dysfunction ,VARIANTS ,pathology [Alzheimer Disease] ,Tau Proteins ,Settore BIO/13 - Biologia Applicata ,Cognitive Dysfunction/psychology ,692/699/375/365/1283 ,IMPUTATION ,article ,1184 Genetics, developmental biology, physiology ,Biología y Biomedicina / Biología ,AMYLOID-BETA ,Settore MED/26 - NEUROLOGIA ,Neurology ,psychology [Cognitive Dysfunction] ,Medical Genetics ,Human ,Neuroscience(all) ,631/208/205/2138 ,All institutes and research themes of the Radboud University Medical Center ,SDG 3 - Good Health and Well-being ,ddc:570 ,Genetics ,Genetic Predisposition to Disease ,GENOME-WIDE ASSOCIATION ,METAANALYSIS ,Medicinsk genetik ,MED/26 - NEUROLOGIA ,Alzheimer Disease/genetics ,neurology ,tau Protein ,NECROSIS-FACTOR-ALPHA ,RISK LOCI ,genetics [tau Proteins] ,PREDICTION MODELS ,Human medicine ,GENERATION ,RESPONSES - Abstract
25 páginas, 6 figuras, 2 tablas, Characterization of the genetic landscape of Alzheimer's disease (AD) and related dementias (ADD) provides a unique opportunity for a better understanding of the associated pathophysiological processes. We performed a two-stage genome-wide association study totaling 111,326 clinically diagnosed/'proxy' AD cases and 677,663 controls. We found 75 risk loci, of which 42 were new at the time of analysis. Pathway enrichment analyses confirmed the involvement of amyloid/tau pathways and highlighted microglia implication. Gene prioritization in the new loci identified 31 genes that were suggestive of new genetically associated processes, including the tumor necrosis factor alpha pathway through the linear ubiquitin chain assembly complex. We also built a new genetic risk score associated with the risk of future AD/dementia or progression from mild cognitive impairment to AD/dementia. The improvement in prediction led to a 1.6- to 1.9-fold increase in AD risk from the lowest to the highest decile, in addition to effects of age and the APOE ε4 allele., This work was funded by a grant (EADB) from the EU Joint Programme – Neurodegenerative Disease Research. INSERM UMR1167 is also funded by the INSERM, Institut Pasteur de Lille, Lille Métropole Communauté Urbaine and French government’s LABEX DISTALZ program (development of innovative strategies for a transdisciplinary approach to AD). Full consortium acknowledgements and funding are in the Supplementary Not
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- 2022
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5. Blocking Excitotoxicity
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Kim, A. H., Kerchner, G. A., Choi, D. W., Marcoux, Frank W., editor, and Choi, Dennis W., editor
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- 2002
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6. Glutamate-Mediated Excitotoxicity
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Kerchner, G. A., Kim, A. H., Choi, D. W., Jonas, Peter, editor, and Monyer, Hannah, editor
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- 1999
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7. Chromosome Xq23 is associated with lower atherogenic lipid concentrations and favorable cardiometabolic indices
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Natarajan, P. (Pradeep), Pampana, A. (Akhil), Graham, S. E. (Sarah E.), Ruotsalainen, S. E. (Sanni E.), Perry, J. A. (James A.), de Vries, P. S. (Paul S.), Broome, J. G. (Jai G.), Pirruccello, J. P. (James P.), Honigbere, M. C. (Michael C.), Aragam, K. (Krishna), Wolford, B. (Brooke), Brody, J. A. (Jennifer A.), Antonacci-Fulton, L. (Lucinda), Arden, M. (Moscati), Aslibekyan, S. (Stella), Assimes, T. L. (Themistocles L.), Ballantyne, C. M. (Christie M.), Bielak, L. F. (Lawrence F.), Bisl, J. C. (Joshua C.), Cade, B. E. (Brian E.), Do, R. (Ron), Doddapaneni, H. (Harsha), Emery, L. S. (Leslie S.), Hung, Y.-J. (Yi-Jen), Irvin, M. R. (Marguerite R.), Khan, A. T. (Alyna T.), Lange, L. (Leslie), Lee, J. (Jiwon), Lemaitre, R. N. (Rozenn N.), Martin, L. W. (Lisa W.), Metcalf, G. (Ginger), Montasser, M. E. (May E.), Moon, J.-Y. (Jee-Young), Muzny, D. (Donna), Connell, J. R. (Jeffrey R. O.), Palmer, N. D. (Nicholette D.), Peralta, J. M. (Juan M.), Peyser, P. A. (Patricia A.), Stilp, A. M. (Adrienne M.), Tsai, M. (Michael), Wang, F. F. (Fei Fei), Weeks, D. E. (Daniel E.), Yanek, L. R. (Lisa R.), Wilson, J. G. (James G.), Abecasis, G. (Goncalo), Arnett, D. K. (Donna K.), Becker, L. C. (Lewis C.), Blangercy, J. (John), Boerwinkle, E. (Eric), Bowden, D. W. (Donald W.), Chang, Y.-C. (Yi-Cheng), Chen, Y. I. (Yii-Der, I), Choi, W. J. (Won Jung), Correa, A. (Adolfo), Curran, J. E. (Joanne E.), Daly, M. J. (Mark J.), DutcherE, S. K. (Susan K.), Ellinor, P. T. (Patrick T.), Fornage, M. (Myriam), Freedman, B. I. (Barry, I), Gabriel, S. (Stacey), Germer, S. (Soren), Gibbs, R. A. (Richard A.), He, J. (Jiang), Hveem, K. (Kristian), Jarvik, G. P. (Gail P.), Kaplan, R. C. (Robert C.), Kardia, S. L. (Sharon L. R.), Kennyn, E. (Eimear), Kim, R. W. (Ryan W.), Kooperberg, C. (Charles), Laurie, C. C. (Cathy C.), Lee, S. (Seonwook), Lloyd-Jones, D. M. (Don M.), Loos, R. J. (Ruth J. F.), Lubitz, S. A. (Steven A.), Mathias, R. A. (Rasika A.), Martinez, K. A. (Karine A. Viaud), McGarvey, S. T. (Stephen T.), Mitche, B. D. (Braxton D.), Nickerson, D. A. (Deborah A.), North, K. E. (Kari E.), Palotie, A. (Aarno), Park, C. J. (Cheol Joo), Psat, B. M. (Bruce M. Y.), Rao, D. C. (D. C.), Redline, S. (Susan), Reiner, A. P. (Alexander P.), Seo, D. (Daekwan), Seo, J.-S. (Jeong-Sun), Smith, A. V. (Albert, V), Tracy, R. P. (Russell P.), Kathiresan, S. (Sekar), Cupples, L. A. (L. Adrienne), Rotten, J. I. (Jerome, I), Morrison, A. C. (Alanna C.), Rich, S. S. (Stephen S.), Ripatti, S. (Samuli), Wilier, C. (Cristen), Peloso, G. M. (Gina M.), Vasan, R. S. (Ramachandran S.), Abe, N. (Namiko), Albert, C. (Christine), Almasy, L. (Laura), Alonso, A. (Alvaro), Ament, S. (Seth), Anderson, P. (Peter), Applebaum-Bowden, D. (Deborah), Arking, D. (Dan), Ashley-Koch, A. (Allison), Auer, P. (Paul), Avramopoulos, D. (Dimitrios), Barnard, J. (John), Barnes, K. (Kathleen), Barr, R. G. (R. Graham), Barron-Casella, E. (Emily), Beaty, T. (Terri), Becker, D. (Diane), Beer, R. (Rebecca), Begum, F. (Ferdouse), Beitelshees, A. (Amber), Benjamin, E. (Emelia), Bezerra, M. (Marcos), Bielak, L. (Larry), Blackwel, T. (Thomas), Bowler, R. (Russell), Broecke, U. (Ulrich), Bunting, K. (Karen), Burchard, E. (Esteban), Buth, E. (Erin), Cardwel, J. (Jonathan), Carty, C. (Cara), Casaburi, R. (Richard), Casella, J. (James), Chaffin, M. (Mark), Chang, C. (Christy), Chasman, D. (Daniel), Chavan, S. (Sameer), Chen, B.-J. (Bo-Juen), Chen, W.-M. (Wei-Min), Chol, M. (Michael), Choi, S. H. (Seung Hoan), Chuang, L.-M. (Lee-Ming), Chung, M. (Mina), Conomos, M. P. (Matthew P.), Cornell, E. (Elaine), Crapo, J. (James), Curtis, J. (Jeffrey), Custer, B. (Brian), Damcott, C. (Coleen), Darbar, D. (Dawood), Das, S. (Sayantan), David, S. (Sean), Davis, C. (Colleen), Daya, M. (Michelle), de Andrade, M. (Mariza), DeBaunuo, M. (Michael), Duan, Q. (Qing), Devine, R. D. (Ranjan Deka Dawn DeMeo Scott), Duggirala, Q. R. (Qing Ravi), Durda, J. P. (Jon Peter), Dutcher, S. (Susan), Eaton, C. (Charles), Ekunwe, L. (Lynette), Farber, C. (Charles), Farnaml, L. (Leanna), Fingerlin, T. (Tasha), Flickinger, M. (Matthew), Franceschini, N. (Nora), Fu, M. (Mao), Fullerton, S. M. (Stephanie M.), Fulton, L. (Lucinda), Gan, W. (Weiniu), Gao, Y. (Yan), Gass, M. (Margery), Ge, B. (Bruce), Geng, X. P. (Xiaoqi Priscilla), Gignoux, C. (Chris), Gladwin, M. (Mark), Glahn, D. (David), Gogarten, S. (Stephanie), Gong, D.-W. (Da-Wei), Goring, H. (Harald), Gu, C. C. (C. Charles), Guan, Y. (Yue), Guo, X. (Xiuqing), Haessler, J. (Jeff), Hall, M. (Michael), Harris, D. (Daniel), Hawle, N. Y. (Nicola Y.), Heavner, B. (Ben), Heckbert, S. (Susan), Hernandez, R. (Ryan), Herrington, D. (David), Hersh, C. (Craig), Hidalgo, B. (Bertha), Hixson, J. (James), Hokanson, J. (John), Hong, E. (Elliott), Hoth, K. (Karin), Hsiung, C. A. (Chao Agnes), Huston, H. (Haley), Hwu, C. M. (Chii Min), Jackson, R. (Rebecca), Jain, D. (Deepti), Jaquish, C. (Cashell), Jhun, M. A. (Min A.), Johnsen, J. (Jill), Johnson, A. (Andrew), Johnson, C. (Craig), Johnston, R. (Rich), Jones, K. (Kimberly), Kang, H. M. (Hyun Min), Kaufman, L. (Laura), Kell, S. Y. (Shannon Y.), Kessler, M. (Michael), Kinney, G. (Greg), Konkle, B. (Barbara), Kramer, H. (Holly), Krauter, S. (Stephanie), Lange, C. (Christoph), Lange, E. (Ethan), Laurie, C. (Cecelia), LeBoff, M. (Meryl), Lee, S. S. (Seunggeun Shawn), Lee, W.-J. (Wen-Jane), LeFaive, J. (Jonathon), Levine, D. (David), Levy, D. (Dan), Lewis, J. (Joshua), Li, Y. (Yun), Lin, H. (Honghuang), Lin, K. H. (Keng Han), Lin, X. (Xihong), Liu, S. (Simin), Liu, Y. (Yongmei), Lunetta, K. (Kathryn), Luo, J. (James), Mahaney, M. (Michael), Make, B. (Barry), Manichaikul, A. (Ani), Mansonl, J. (JoAnn), Margolin, L. (Lauren), Mathai, S. (Susan), McArdle, P. (Patrick), Mcdonald, M.-L. (Merry-Lynn), McFarland, S. (Sean), McHugh, C. (Caitlin), Mei, H. (Hao), Meyers, D. A. (Deborah A.), Mikulla, J. (Julie), Min, N. (Nancy), Minear, M. (Mollie), Minster, R. L. (Ryan L.), Musani, S. (Solomon), Mwasongwe, S. (Stanford), Mychaleckyj, J. C. (Josyf C.), Nadkarni, G. (Girish), Naik, R. (Rakhi), Naseri, T. (Take), Nekhai, S. (Sergei), Nelson, S. C. (Sarah C.), Nickerson, D. (Deborah), Connell, J. O. (Jeff O.), Connor, T. O. (Tim O.), Ochs-Balcom, H. (Heather), Pankow, J. (James), Papanicolaou, G. (George), Parkerl, M. (Margaret), Parsa, A. (Afshin), Penchey, S. (Sara), Perez, M. (Marco), Peters, U. (Ulrike), Phillips, L. S. (Lawrence S.), Phillips, S. (Sam), Pollin, T. (Toni), Post, W. (Wendy), Becker, J. P. (Julia Powers), Boorgula, M. P. (Meher Preethi), Preuss, M. (Michael), Prokopenko, D. (Dmitry), Qasba, P. (Pankaj), Qiao, D. (Dandi), Rafaels, N. (Nicholas), Raffield, L. (Laura), Rasmussen-Torvik, L. (Laura), Ratan, A. (Aakrosh), Reed, R. (Robert), Reganl, E. (Elizabeth), Reupena, M. S. (Muagututi Sefuiva), Rice, K. (Ken), Roden, D. (Dan), Roselli, C. (Carolina), Ruczinski, I. (Ingo), Russel, P. (Pamela), Ruuska, S. (Sarah), Ryan, K. (Kathleen), Sabino, E. C. (Ester Cerdeira), Sakornsakolpatl, P. (Phuwanat), Salzberg, S. (Steven), Sandow, K. (Kevin), Sankaran, V. G. (Vijay G.), Scheller, C. (Christopher), Schmidt, E. (Ellen), Schwander, K. (Karen), Schwartz, D. (David), Sciurba, F. (Frank), Seidman, C. (Christine), Seidman, J. (Jonathan), Sheehan, V. (Vivien), Shetty, A. (Amol), Shetty, A. (Aniket), Sheu, W. H. (Wayne Hui-Heng), Shoemaker, M. B. (M. Benjamin), Silver, B. (Brian), Silvermanl, E. (Edwin), Smith, J. (Jennifer), Smith, J. (Josh), Smith, N. (Nicholas), Smith, T. (Tanja), Smoller, S. (Sylvia), Snively, B. (Beverly), Soferlm, T. (Tamar), Streeten, E. (Elizabeth), Su, J. L. (Jessica Lasky), Sung, Y. J. (Yun Ju), Sylvia, J. (Jody), Sztalryd, C. (Carole), Taliun, D. (Daniel), Tang, H. (Hua), Taub, M. (Margaret), Taylor, K. D. (Kent D.), Taylor, S. (Simeon), Telen, M. (Marilyn), Thornton, T. A. (Timothy A.), Tinker, L. (Lesley), Tirschwel, D. (David), Tiwari, H. (Hemant), Vaidya, D. (Dhananjay), VandeHaar, P. (Peter), Vrieze, S. (Scott), Walker, T. (Tarik), Wallace, R. (Robert), Waits, A. (Avram), Wan, E. (Emily), Wang, H. (Heming), Watson, K. (Karol), Weir, B. (Bruce), Weiss, S. (Scott), Weng, L.-C. (Lu-Chen), Williams, K. (Kayleen), Williams, L. K. (L. Keoki), Wilson, C. (Carla), Wong, Q. (Quenna), Xu, H. (Huichun), Yang, I. (Ivana), Yang, R. (Rongze), Zaghlou, N. (Norann), Zekavat, M. (Maryam), Zhang, Y. (Yingze), Zhao, S. X. (Snow Xueyan), Zhao, W. (Wei), Zni, D. (Degui), Zhou, X. (Xiang), Zhu, X. (Xiaofeng), Zody, M. (Michael), Zoellner, S. (Sebastian), Daly, M. (Mark), Jacob, H. (Howard), Matakidou, A. (Athena), Runz, H. (Heiko), John, S. (Sally), Plenge, R. (Robert), McCarthy, M. (Mark), Hunkapiller, J. (Julie), Ehm, M. (Meg), Waterworth, D. (Dawn), Fox, C. (Caroline), Malarstig, A. (Anders), Klinger, K. (Kathy), Call, K. (Kathy), Mkel, T. (Tomi), Kaprio, J. (Jaakko), Virolainen, P. (Petri), Pulkki, K. (Kari), Kilpi, T. (Terhi), Perola, M. (Markus), Partanen, J. (Jukka), Pitkranta, A. (Anne), Kaarteenaho, R. (Riitta), Vainio, S. (Seppo), Savinainen, K. (Kimmo), Kosma, V.-M. (Veli-Matti), Kujala, U. (Urho), Tuovila, O. (Outi), Hendolin, M. (Minna), Pakkanen, R. (Raimo), Waring, J. (Jeff), Riley-Gillis, B. (Bridget), Liu, J. (Jimmy), Biswas, S. (Shameek), Diogo, D. (Dorothee), Marshall, C. (Catherine), Hu, X. (Xinli), Gossel, M. (Matthias), Schleutker, J. (Johanna), Arvas, M. (Mikko), Hinttala, R. (Reetta), Kettunen, J. (Johannes), Laaksonen, R. (Reijo), Mannermaa, A. (Arto), Paloneva, J. (Juha), Soininen, H. (Hilkka), Julkunen, V. (Valtteri), Remes, A. (Anne), Klviinen, R. (Reetta), Hiltunen, M. (Mikko), Peltola, J. (Jukka), Tienari, P. (Pentti), Rinne, J. (Juha), Ziemann, A. (Adam), Waring, J. (Jeffrey), Esmaeeli, S. (Sahar), Smaoui, N. (Nizar), Lehtonen, A. (Anne), Eaton, S. (Susan), Landenper, S. (Sanni), Michon, J. (John), Kerchner, G. (Geoff), Bowers, N. (Natalie), Teng, E. (Edmond), Eicher, J. (John), Mehta, V. (Vinay), Gormle, P. Y. (Padhraig Y.), Linden, K. (Kari), Whelan, C. (Christopher), Xu, F. (Fanli), Pulford, D. (David), Frkkil, M. (Martti), Pikkarainen, S. (Sampsa), Jussila, A. (Airi), Blomster, T. (Timo), Kiviniemi, M. (Mikko), Voutilainen, M. (Markku), Georgantas, B. (Bob), Heap, G. (Graham), Rahimov, F. (Fedik), Usiskin, K. (Keith), Maranville, J. (Joseph), Lu, T. (Tim), Oh, D. (Danny), Kalpala, K. (Kirsi), Miller, M. (Melissa), McCarthy, L. (Linda), Eklund, K. (Kari), Palomki, A. (Antti), Isomki, P. (Pia), Piri, L. (Laura), Kaipiainen-Seppnen, O. (Oili), Lertratanaku, A. (Apinya), Bing, D. C. (David Close Marla Hochfeld Nan), Gordillo, J. E. (Jorge Esparza), Mars, N. (Nina), Laitinen, T. (Tarja), Pelkonen, M. (Margit), Kauppi, P. (Paula), Kankaanranta, H. (Hannu), Harju, T. (Terttu), Greenberg, S. (Steven), Chen, H. (Hubert), Betts, J. (Jo), Ghosh, S. (Soumitra), Salomaa, V. (Veikko), Niiranen, T. (Teemu), Juonala, M. (Markus), Metsrinne, K. (Kaj), Khnen, M. (Mika), Junttila, J. (Juhani), Laakso, M. (Markku), Pihlajamki, J. (Jussi), Sinisalo, J. (Juha), Taskinen, M.-R. (Marja-Riitta), Tuomi, T. (Tiinamaija), Laukkanen, J. (Jari), Challis, B. (Ben), Peterson, A. (Andrew), Chu, A. (Audrey), Parkkinen, J. (Jaakko), Muslin, A. (Anthony), Joensuu, H. (Heikki), Meretoja, T. (Tuomo), Aaltonen, L. (Lauri), Auranen, A. (Annika), Karihtala, P. (Peeter), Kauppila, S. (Saila), Auvinen, P. (Pivi), Elenius, K. (Klaus), Popovic, R. (Relja), Schutzman, J. (Jennifer), Loboda, A. (Andrey), Chhibber, A. (Aparna), Lehtonen, H. (Heli), McDonough, S. (Stefan), Crohns, M. (Marika), Kulkarni, D. (Diptee), Kaarniranta, K. (Kai), Turunen, J. (Joni), Ollila, T. (Terhi), Seitsonen, S. (Sanna), Uusitalo, H. (Hannu), Aaltonen, V. (Vesa), Uusitalo-Jrvinen, H. (Hannele), Luodonp, M. (Marja), Hautala, N. (Nina), Strauss, E. (Erich), Chen, H. (Hao), Podgornaia, A. (Anna), Hoffman, J. (Joshua), Tasanen, K. (Kaisa), Huilaja, L. (Laura), Hannula-Jouppi, K. (Katariina), Salmi, T. (Teea), Peltonen, S. (Sirkku), Koulu, L. (Leena), Harvima, I. (Ilkka), Wu, Y. (Ying), Choy, D. (David), Jalanko, A. (Anu), Kajanne, R. (Risto), Lyhs, U. (Ulrike), Kaunisto, M. (Mari), Davis, J. W. (Justin Wade), Quarless, D. (Danjuma), Petrovski, S. (Slav), Chen, C.-Y. (Chia-Yen), Bronson, P. (Paola), Yang, R. (Robert), Chang, D. (Diana), Bhangale, T. (Tushar), Holzinger, E. (Emily), Wang, X. (Xulong), Chen, X. (Xing), Auro, K. (Kirsi), Wang, C. (Clarence), Xu, E. (Ethan), Auge, F. (Franck), Chatelain, C. (Clement), Kurki, M. (Mitja), Karjalainen, J. (Juha), Havulinna, A. (Aki), Palin, K. (Kimmo), Palta, P. (Priit), Parolo, P. D. (Pietro Della Briotta), Zhou, W. (Wei), Lemmel, S. (Susanna), Rivas, M. (Manuel), Harju, J. (Jarmo), Lehisto, A. (Arto), Ganna, A. (Andrea), Llorens, V. (Vincent), Karlsson, A. (Antti), Kristiansson, K. (Kati), Hyvrinen, K. (Kati), Ritari, J. (Jarmo), Wahlfors, T. (Tiina), Koskinen, M. (Miika), Pylkäs, K. (Katri), Kalaoja, M. (Marita), Karjalainen, M. (Minna), Mantere, T. (Tuomo), Kangasniemi, E. (Eeva), Heikkinen, S. (Sami), Laakkonen, E. (Eija), Kononen, J. (Juha), Loukola, A. (Anu), Laiho, P. (Pivi), Sistonen, T. (Tuuli), Kaiharju, E. (Essi), Laukkanen, M. (Markku), Jrvensivu, E. (Elina), Lhteenmki, S. (Sini), Mnnikk, L. (Lotta), Wong, R. (Regis), Mattsson, H. (Hannele), Hiekkalinna, T. (Tero), Jimnez, M. G. (Manuel Gonzlez), Donner, K. (Kati), Prn, K. (KaIle), Nunez-Fontarnau, J. (Javier), Kilpelinen, E. (Elina), Sipi, T. P. (Timo P.), Brein, G. (Georg), Dada, A. (Alexander), Awaisa, G. (Ghazal), Shcherban, A. (Anastasia), Sipil, T. (Tuomas), Laivuori, H. (Hannele), Kiiskinen, T. (Tuomo), Siirtola, H. (Harri), Tabuenca, J. G. (Javier Gracia), Kallio, L. (Lila), Soini, S. (Sirpa), Pitknen, K. (Kimmo), and Kuopio, T. (Teijo)
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Cardiovascular genetics ,Genome-wide association studies - Abstract
Autosomal genetic analyses of blood lipids have yielded key insights for coronary heart disease (CHD). However, X chromosome genetic variation is understudied for blood lipids in large sample sizes. We now analyze genetic and blood lipid data in a high-coverage whole X chromosome sequencing study of 65,322 multi-ancestry participants and perform replication among 456,893 European participants. Common alleles on chromosome Xq23 are strongly associated with reduced total cholesterol, LDL cholesterol, and triglycerides (min P = 8.5 × 10−72), with similar effects for males and females. Chromosome Xq23 lipid-lowering alleles are associated with reduced odds for CHD among 42,545 cases and 591,247 controls (P = 1.7 × 10−4), and reduced odds for diabetes mellitus type 2 among 54,095 cases and 573,885 controls (P = 1.4 × 10−5). Although we observe an association with increased BMI, waist-to-hip ratio adjusted for BMI is reduced, bioimpedance analyses indicate increased gluteofemoral fat, and abdominal MRI analyses indicate reduced visceral adiposity. Co-localization analyses strongly correlate increased CHRDL1 gene expression, particularly in adipose tissue, with reduced concentrations of blood lipids.
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- 2021
8. Blocking Excitotoxicity
- Author
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Kim, A. H., primary, Kerchner, G. A., additional, and Choi, D. W., additional
- Published
- 2002
- Full Text
- View/download PDF
9. Glutamate-Mediated Excitotoxicity
- Author
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Kerchner, G. A., primary, Kim, A. H., additional, and Choi, D. W., additional
- Published
- 1999
- Full Text
- View/download PDF
10. Genetic architecture of human plasma lipidome and its link to cardiovascular disease
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Tabassum, R. (Rubina), Ramo, J. T. (Joel T.), Ripatti, P. (Pietari), Koskela, J. T. (Jukka T.), Kurki, M. (Mitja), Karjalainen, J. (Juha), Palta, P. (Priit), Hassan, S. (Shabbeer), Nunez-Fontarnau, J. (Javier), Kiiskinen, T. T. (Tuomo T. J.), Soderlund, S. (Sanni), Matikainen, N. (Niina), Gerl, M. J. (Mathias J.), Surma, M. A. (Michal A.), Klose, C. (Christian), Stitziel, N. O. (Nathan O.), Laivuori, H. (Hannele), Havulinna, A. S. (Aki S.), Service, S. K. (Susan K.), Salomaa, V. (Veikko), Pirinen, M. (Matti), Jauhiainen, M. (Matti), Daly, M. J. (Mark J.), Freimer, N. B. (Nelson B.), Palotie, A. (Aarno), Taskinen, M.-R. (Marja-Riitta), Simons, K. (Kai), Ripatti, S. (Samuli), Jalanko, A. (Anu), Kaprio, J. (Jaakko), Donner, K. (Kati), Kaunisto, M. (Mari), Mars, N. (Nina), Dada, A. (Alexander), Shcherban, A. (Anastasia), Ganna, A. (Andrea), Lehisto, A. (Arto), Kilpelainen, E. (Elina), Brein, G. (Georg), Awaisa, G. (Ghazal), Harju, J. (Jarmo), Parr, K. (Kalle), Parolo, P. D. (Pietro Della Briotta), Kajanne, R. (Risto), Lemmela, S. (Susanna), Sipila, T. P. (Timo P.), Sipila, T. (Tuomas), Lyhs, U. (Ulrike), Llorens, V. (Vincent), Niiranen, T. (Teemu), Kristiansson, K. (Kati), Mannikko, L. (Lotta), Jimenez, M. G. (Manuel Gonzalez), Perola, M. (Markus), Wong, R. (Regis), Kilpi, T. (Terhi), Hiekkalinna, T. (Tero), Jarvensivu, E. (Elina), Kaiharju, E. (Essi), Mattsson, H. (Hannele), Laukkanen, M. (Markku), Laiho, P. (Paivi), Lahteenmaki, S. (Sini), Sistonen, T. (Tuuli), Soini, S. (Sirpa), Ziemann, A. (Adam), Lehtonen, A. (Anne), Lertratanakul, A. (Apinya), Georgantas, B. (Bob), Riley-Gillis, B. (Bridget), Quarless, D. (Danjuma), Rahimov, F. (Fedik), Heap, G. (Graham), Jacob, H. (Howard), Waring, J. (Jeffrey), Davis, J. W. (Justin Wade), Smaoui, N. (Nizar), Popovic, R. (Relja), Esmaeeli, S. (Sahar), Waring, J. (Jeff), Matakidou, A. (Athena), Challis, B. (Ben), Close, D. (David), Petrovski, S. (Slave), Karlsson, A. (Antti), Schleutker, J. (Johanna), Pulkki, K. (Kari), Virolainen, P. (Petri), Kallio, L. (Lila), Mannermaa, A. (Arto), Heikkinen, S. (Sami), Kosma, V.-M. (Veli-Matti), Chen, C.-Y. (Chia-Yen), Runz, H. (Heiko), Liu, J. (Jimmy), Bronson, P. (Paola), John, S. (Sally), Landenpera, S. (Sanni), Eaton, S. (Susan), Zhou, W. (Wei), Hendolin, M. (Minna), Tuovila, O. (Outi), Pakkanen, R. (Raimo), Maranville, J. (Joseph), Usiskin, K. (Keith), Hochfeld, M. (Marla), Plenge, R. (Robert), Yang, R. (Robert), Biswas, S. (Shameek), Greenberg, S. (Steven), Laakkonen, E. (Eija), Kononen, J. (Juha), Paloneva, J. (Juha), Kujala, U. (Urho), Kuopio, T. (Teijo), Laukkanen, J. (Jari), Kangasniemi, E. (Eeva), Savinainen, K. (Kimmo), Laaksonen, R. (Reijo), Arvas, M. (Mikko), Ritari, J. (Jarmo), Partanen, J. (Jukka), Hyvarinen, K. (Kati), Wahlfors, T. (Tiina), Peterson, A. (Andrew), Oh, D. (Danny), Chang, D. (Diana), Teng, E. (Edmond), Strauss, E. (Erich), Kerchner, G. (Geoff), Chen, H. (Hao), Chen, H. (Hubert), Schutzman, J. (Jennifer), Michon, J. (John), Hunkapiller, J. (Julie), McCarthy, M. (Mark), Bowers, N. (Natalie), Lu, T. (Tim), Bhangale, T. (Tushar), Pulford, D. (David), Waterworth, D. (Dawn), Kulkarni, D. (Diptee), Xu, F. (Fanli), Betts, J. (Jo), Gordillo, J. E. (Jorge Esparza), Hoffman, J. (Joshua), Auro, K. (Kirsi), McCarthy, L. (Linda), Ghosh, S. (Soumitra), Ehm, M. (Meg), Pitkanen, K. (Kimmo), Makela, T. (Tomi), Loukola, A. (Anu), Joensuu, H. (Heikki), Sinisalo, J. (Juha), Eklund, K. (Kari), Aaltonen, L. (Lauri), Farkkila, M. (Martti), Carpen, O. (Olli), Kauppi, P. (Paula), Tienari, P. (Pentti), Ollila, T. (Terhi), Tuomi, T. (Tiinamaija), Meretoja, T. (Tuomo), Pitkaranta, A. (Anne), Turunen, J. (Joni), Hannula-Jouppi, K. (Katariina), Pikkarainen, S. (Sampsa), Seitsonen, S. (Sanna), Koskinen, M. (Miika), Palomaki, A. (Antti), Rinne, J. (Juha), Metsarinne, K. (Kaj), Elenius, K. (Klaus), Pirila, L. (Laura), Koulu, L. (Leena), Voutilainen, M. (Markku), Juonala, M. (Markus), Peltonen, S. (Sirkku), Aaltonen, V. (Vesa), Loboda, A. (Andrey), Podgornaia, A. (Anna), Chhibber, A. (Aparna), Chu, A. (Audrey), Fox, C. (Caroline), Diogo, D. (Dorothee), Holzinger, E. (Emily), Eicher, J. (John), Gormley, P. (Padhraig), Mehta, V. (Vinay), Wang, X. (Xulong), Kettunen, J. (Johannes), Pylkas, K. (Katri), Kalaoja, M. (Marita), Karjalainen, M. (Minna), Hinttala, R. (Reetta), Kaarteenaho, R. (Riitta), Vainio, S. (Seppo), Mantere, T. (Tuomo), Remes, A. (Anne), Huhtakangas, J. (Johanna), Junttila, J. (Juhani), Tasanen, K. (Kaisa), Huilaja, L. (Laura), Luodonpaa, M. (Marja), Hautala, N. (Nina), Karihtala, P. (Peeter), Kauppila, S. (Saila), Harju, T. (Terttu), Blomster, T. (Timo), Soininen, H. (Hilkka), Harvima, I. (Ilkka), Pihlajamaki, J. (Jussi), Kaarniranta, K. (Kai), Pelkonen, M. (Margit), Laakso, M. (Markku), Hiltunen, M. (Mikko), Kiviniemi, M. (Mikko), Kaipiainen-Seppanen, O. (Oili), Auvinen, P. (Paivi), Kalviainen, R. (Reetta), Julkunen, V. (Valtteri), Malarstig, A. (Anders), Hedman, A. (Asa), Marshal, C. (Catherine), Whelan, C. (Christopher), Lehtonen, H. (Heli), Parkkinen, J. (Jaakko), Linden, K. (Kari), Kalpala, K. (Kirsi), Miller, M. (Melissa), Bing, N. (Nan), McDonough, S. (Stefan), Chen, X. (Xing), Hu, X. (Xinli), Wu, Y. (Ying), Auranen, A. (Annika), Jussila, A. (Airi), Uusitalo-Jarvinen, H. (Hannele), Kankaanranta, H. (Hannu), Uusitalo, H. (Hannu), Peltola, J. (Jukka), Kahonen, M. (Mika), Isomaki, P. (Pia), Laitinen, T. (Tarja), Salmi, T. (Teea), Muslin, A. (Anthony), Wang, C. (Clarence), Chatelain, C. (Clement), Xu, E. (Ethan), Auge, F. (Franck), Call, K. (Kathy), Klinger, K. (Kathy), Crohns, M. (Marika), Gossel, M. (Matthias), Palin, K. (Kimmo), Rivas, M. (Manuel), Siirtola, H. (Harri), and Tabuenca, J. G. (Javier Gracia)
- Subjects
lipids (amino acids, peptides, and proteins) - Abstract
Understanding genetic architecture of plasma lipidome could provide better insights into lipid metabolism and its link to cardiovascular diseases (CVDs). Here, we perform genome-wide association analyses of 141 lipid species (n = 2,181 individuals), followed by phenome-wide scans with 25 CVD related phenotypes (n = 511,700 individuals). We identify 35 lipid-species-associated loci (P
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- 2019
11. Genetic architecture of human plasma lipidome and its link to cardiovascular disease
- Author
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Tabassum, R, Ramo, JT, Ripatti, P, Koskela, JT, Kurki, M, Karjalainen, J, Palta, P, Hassan, S, Nunez-Fontarnau, J, Kiiskinen, TTJ, Soderlund, S, Matikainen, N, Gerl, MJ, Surma, MA, Klose, C, Stitziel, NO, Laivuori, H, Havulinna, AS, Service, SK, Salomaa, V, Pirinen, M, Jauhiainen, M, Daly, MJ, Freimer, NB, Palotie, A, Taskinen, M-R, Simons, K, Ripatti, S, Jalanko, A, Kaprio, J, Donner, K, Kaunisto, M, Mars, N, Dada, A, Shcherban, A, Ganna, A, Lehisto, A, Kilpelainen, E, Brein, G, Awaisa, G, Harju, J, Parr, K, Parolo, PDB, Kajanne, R, Lemmela, S, Sipila, TP, Sipila, T, Lyhs, U, Llorens, V, Niiranen, T, Kristiansson, K, Mannikko, L, Jimenez, MG, Perola, M, Wong, R, Kilpi, T, Hiekkalinna, T, Jarvensivu, E, Kaiharju, E, Mattsson, H, Laukkanen, M, Laiho, P, Lahteenmaki, S, Sistonen, T, Soini, S, Ziemann, A, Lehtonen, A, Lertratanakul, A, Georgantas, B, Riley-Gillis, B, Quarless, D, Rahimov, F, Heap, G, Jacob, H, Waring, J, Davis, JW, Smaoui, N, Popovic, R, Esmaeeli, S, Matakidou, A, Challis, B, Close, D, Petrovski, S, Karlsson, A, Schleutker, J, Pulkki, K, Virolainen, P, Kallio, L, Mannermaa, A, Heikkinen, S, Kosma, V-M, Chen, C-Y, Runz, H, Liu, J, Bronson, P, John, S, Landenpera, S, Eaton, S, Zhou, W, Hendolin, M, Tuovila, O, Pakkanen, R, Maranville, J, Usiskin, K, Hochfeld, M, Plenge, R, Yang, R, Biswas, S, Greenberg, S, Laakkonen, E, Kononen, J, Paloneva, J, Kujala, U, Kuopio, T, Laukkanen, J, Kangasniemi, E, Savinainen, K, Laaksonen, R, Arvas, M, Ritari, J, Partanen, J, Hyvarinen, K, Wahlfors, T, Peterson, A, Oh, D, Chang, D, Teng, E, Strauss, E, Kerchner, G, Chen, H, Schutzman, J, Michon, J, Hunkapiller, J, McCarthy, M, Bowers, N, Lu, T, Bhangale, T, Pulford, D, Waterworth, D, Kulkarni, D, Xu, F, Betts, J, Gordillo, JE, Hoffman, J, Auro, K, McCarthy, L, Ghosh, S, Ehm, M, Pitkanen, K, Makela, T, Loukola, A, Joensuu, H, Sinisalo, J, Eklund, K, Aaltonen, L, Farkkila, M, Carpen, O, Kauppi, P, Tienari, P, Ollila, T, Tuomi, T, Meretoja, T, Pitkaranta, A, Turunen, J, Hannula-Jouppi, K, Pikkarainen, S, Seitsonen, S, Koskinen, M, Palomaki, A, Rinne, J, Metsarinne, K, Elenius, K, Pirila, L, Koulu, L, Voutilainen, M, Juonala, M, Peltonen, S, Aaltonen, V, Loboda, A, Podgornaia, A, Chhibber, A, Chu, A, Fox, C, Diogo, D, Holzinger, E, Eicher, J, Gormley, P, Mehta, V, Wang, X, Kettunen, J, Pylkas, K, Kalaoja, M, Karjalainen, M, Hinttala, R, Kaarteenaho, R, Vainio, S, Mantere, T, Remes, A, Huhtakangas, J, Junttila, J, Tasanen, K, Huilaja, L, Luodonpaa, M, Hautala, N, Karihtala, P, Kauppila, S, Harju, T, Blomster, T, Soininen, H, Harvima, I, Pihlajamaki, J, Kaarniranta, K, Pelkonen, M, Laakso, M, Hiltunen, M, Kiviniemi, M, Kaipiainen-Seppanen, O, Auvinen, P, Kalviainen, R, Julkunen, V, Malarstig, A, Hedman, A, Marshal, C, Whelan, C, Lehtonen, H, Parkkinen, J, Linden, K, Kalpala, K, Miller, M, Bing, N, McDonough, S, Chen, X, Hu, X, Wu, Y, Auranen, A, Jussila, A, Uusitalo-Jarvinen, H, Kankaanranta, H, Uusitalo, H, Peltola, J, Kahonen, M, Isomaki, P, Laitinen, T, Salmi, T, Muslin, A, Wang, C, Chatelain, C, Xu, E, Auge, F, Call, K, Klinger, K, Crohns, M, Gossel, M, Palin, K, Rivas, M, Siirtola, H, Tabuenca, JG, Tabassum, R, Ramo, JT, Ripatti, P, Koskela, JT, Kurki, M, Karjalainen, J, Palta, P, Hassan, S, Nunez-Fontarnau, J, Kiiskinen, TTJ, Soderlund, S, Matikainen, N, Gerl, MJ, Surma, MA, Klose, C, Stitziel, NO, Laivuori, H, Havulinna, AS, Service, SK, Salomaa, V, Pirinen, M, Jauhiainen, M, Daly, MJ, Freimer, NB, Palotie, A, Taskinen, M-R, Simons, K, Ripatti, S, Jalanko, A, Kaprio, J, Donner, K, Kaunisto, M, Mars, N, Dada, A, Shcherban, A, Ganna, A, Lehisto, A, Kilpelainen, E, Brein, G, Awaisa, G, Harju, J, Parr, K, Parolo, PDB, Kajanne, R, Lemmela, S, Sipila, TP, Sipila, T, Lyhs, U, Llorens, V, Niiranen, T, Kristiansson, K, Mannikko, L, Jimenez, MG, Perola, M, Wong, R, Kilpi, T, Hiekkalinna, T, Jarvensivu, E, Kaiharju, E, Mattsson, H, Laukkanen, M, Laiho, P, Lahteenmaki, S, Sistonen, T, Soini, S, Ziemann, A, Lehtonen, A, Lertratanakul, A, Georgantas, B, Riley-Gillis, B, Quarless, D, Rahimov, F, Heap, G, Jacob, H, Waring, J, Davis, JW, Smaoui, N, Popovic, R, Esmaeeli, S, Matakidou, A, Challis, B, Close, D, Petrovski, S, Karlsson, A, Schleutker, J, Pulkki, K, Virolainen, P, Kallio, L, Mannermaa, A, Heikkinen, S, Kosma, V-M, Chen, C-Y, Runz, H, Liu, J, Bronson, P, John, S, Landenpera, S, Eaton, S, Zhou, W, Hendolin, M, Tuovila, O, Pakkanen, R, Maranville, J, Usiskin, K, Hochfeld, M, Plenge, R, Yang, R, Biswas, S, Greenberg, S, Laakkonen, E, Kononen, J, Paloneva, J, Kujala, U, Kuopio, T, Laukkanen, J, Kangasniemi, E, Savinainen, K, Laaksonen, R, Arvas, M, Ritari, J, Partanen, J, Hyvarinen, K, Wahlfors, T, Peterson, A, Oh, D, Chang, D, Teng, E, Strauss, E, Kerchner, G, Chen, H, Schutzman, J, Michon, J, Hunkapiller, J, McCarthy, M, Bowers, N, Lu, T, Bhangale, T, Pulford, D, Waterworth, D, Kulkarni, D, Xu, F, Betts, J, Gordillo, JE, Hoffman, J, Auro, K, McCarthy, L, Ghosh, S, Ehm, M, Pitkanen, K, Makela, T, Loukola, A, Joensuu, H, Sinisalo, J, Eklund, K, Aaltonen, L, Farkkila, M, Carpen, O, Kauppi, P, Tienari, P, Ollila, T, Tuomi, T, Meretoja, T, Pitkaranta, A, Turunen, J, Hannula-Jouppi, K, Pikkarainen, S, Seitsonen, S, Koskinen, M, Palomaki, A, Rinne, J, Metsarinne, K, Elenius, K, Pirila, L, Koulu, L, Voutilainen, M, Juonala, M, Peltonen, S, Aaltonen, V, Loboda, A, Podgornaia, A, Chhibber, A, Chu, A, Fox, C, Diogo, D, Holzinger, E, Eicher, J, Gormley, P, Mehta, V, Wang, X, Kettunen, J, Pylkas, K, Kalaoja, M, Karjalainen, M, Hinttala, R, Kaarteenaho, R, Vainio, S, Mantere, T, Remes, A, Huhtakangas, J, Junttila, J, Tasanen, K, Huilaja, L, Luodonpaa, M, Hautala, N, Karihtala, P, Kauppila, S, Harju, T, Blomster, T, Soininen, H, Harvima, I, Pihlajamaki, J, Kaarniranta, K, Pelkonen, M, Laakso, M, Hiltunen, M, Kiviniemi, M, Kaipiainen-Seppanen, O, Auvinen, P, Kalviainen, R, Julkunen, V, Malarstig, A, Hedman, A, Marshal, C, Whelan, C, Lehtonen, H, Parkkinen, J, Linden, K, Kalpala, K, Miller, M, Bing, N, McDonough, S, Chen, X, Hu, X, Wu, Y, Auranen, A, Jussila, A, Uusitalo-Jarvinen, H, Kankaanranta, H, Uusitalo, H, Peltola, J, Kahonen, M, Isomaki, P, Laitinen, T, Salmi, T, Muslin, A, Wang, C, Chatelain, C, Xu, E, Auge, F, Call, K, Klinger, K, Crohns, M, Gossel, M, Palin, K, Rivas, M, Siirtola, H, and Tabuenca, JG
- Abstract
Understanding genetic architecture of plasma lipidome could provide better insights into lipid metabolism and its link to cardiovascular diseases (CVDs). Here, we perform genome-wide association analyses of 141 lipid species (n = 2,181 individuals), followed by phenome-wide scans with 25 CVD related phenotypes (n = 511,700 individuals). We identify 35 lipid-species-associated loci (P <5 ×10-8), 10 of which associate with CVD risk including five new loci-COL5A1, GLTPD2, SPTLC3, MBOAT7 and GALNT16 (false discovery rate<0.05). We identify loci for lipid species that are shown to predict CVD e.g., SPTLC3 for CER(d18:1/24:1). We show that lipoprotein lipase (LPL) may more efficiently hydrolyze medium length triacylglycerides (TAGs) than others. Polyunsaturated lipids have highest heritability and genetic correlations, suggesting considerable genetic regulation at fatty acids levels. We find low genetic correlations between traditional lipids and lipid species. Our results show that lipidomic profiles capture information beyond traditional lipids and identify genetic variants modifying lipid levels and risk of CVD.
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- 2019
12. Thirty-Six-Month Amyloid Positron Emission Tomography Results Show Continued Reduction in Amyloid Burden with Subcutaneous Gantenerumab.
- Author
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Klein, Gregory, Delmar, P., Kerchner, G. A., Hofmann, C., Abi-Saab, D., Davis, A., Voyle, N., Baudler, M., Fontoura, P., and Doody, R.
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- 2020
- Full Text
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13. APOE 4 worsens hippocampal CA1 apical neuropil atrophy and episodic memory
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Kerchner, G. A., primary, Berdnik, D., additional, Shen, J. C., additional, Bernstein, J. D., additional, Fenesy, M. C., additional, Deutsch, G. K., additional, Wyss-Coray, T., additional, and Rutt, B. K., additional
- Published
- 2014
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14. Shared Vulnerability of Two Synaptically-Connected Medial Temporal Lobe Areas to Age and Cognitive Decline: A Seven Tesla Magnetic Resonance Imaging Study
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Kerchner, G. A., primary, Bernstein, J. D., additional, Fenesy, M. C., additional, Deutsch, G. K., additional, Saranathan, M., additional, Zeineh, M. M., additional, and Rutt, B. K., additional
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- 2013
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15. From Alois to Amyvid: Seeing Alzheimer disease
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Furst, A. J., primary and Kerchner, G. A., additional
- Published
- 2012
- Full Text
- View/download PDF
16. Hippocampal CA1 Apical Neuropil Atrophy and Memory Performance in Alzheimer Disease (P04.223)
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Kerchner, G., primary, Deutsch, G., additional, Zeineh, M., additional, Dougherty, R., additional, and Rutt, B., additional
- Published
- 2012
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17. Hippocampal CA1 apical neuropil atrophy in mild Alzheimer disease visualized with 7-T MRI
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Kerchner, G. A., primary, Hess, C. P., additional, Hammond-Rosenbluth, K. E., additional, Xu, D., additional, Rabinovici, G. D., additional, Kelley, D. A. C., additional, Vigneron, D. B., additional, Nelson, S. J., additional, and Miller, B. L., additional
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- 2010
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18. Co-occurrence of a cavernous malformation and contralateral moyamoya
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Kerchner, G. A., primary, Smith, W., additional, Lawton, M. T., additional, and Singh, V., additional
- Published
- 2006
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19. Sigma opioid receptor: characterization and co-identity with the phencyclidine receptor.
- Author
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Mendelsohn, L G, Kalra, V, Johnson, B G, and Kerchner, G A
- Abstract
The properties of the sigma opioid receptor of rat brain cortex have been characterized using the prototypic ligand (+)-[3H] SKF 10,047. Binding to this receptor was rapid, and equilibrium was obtained within 30 min at 37 degrees C. Specific binding was linear with protein concentration up to 500 micrograms/2 ml and was dependent upon protein integrity. Denaturation by boiling destroyed over 95% of the specific binding. A high-affinity binding site with a KD of 150 +/- 40 nM and a maximum binding of 2.91 +/- 0.84 pmol/mg of protein was determined from a Scatchard plot of the binding data. The addition of salt, either NaCl or CaCl2, to the buffers markedly decreased binding, with CaCl2 being more potent than NaCl. A broad pH optimum for specific binding was observed; maximum binding was at pH 9.0. The affinity of a number of ligands for the sigma site and the phencyclidine receptor were compared. The binding (IC50) of 13 ligands to the sigma site showed a correlation of 0.86 (P less than .01) with binding to the phencyclidine site. The data demonstrate that the biochemical properties of the sigma and phencyclidine receptors are similar and support the view that these receptors are one and the same site.
- Published
- 1985
20. Characterization of the hepatic microsomal mixed-function oxidase enzyme system in miniature pigs.
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Freudenthal, R I, Leber, P, Emmerling, D, Kerchner, G, and Campbell, D
- Abstract
Hepatic microsomal protein, cytochrome P-450, UDP-glucuronyltransferase, ethylmorphine demethylase, aniline hydroxylase, and aryl hydrocarbon hydroxylase levels were measured in the 2-, 4-, 5-, 6-, and 8-month-old Hanford miniature pig. The activities or concentrations of all of the liver parameters measured had apparently reached their adult plateau level by 2 months of age. The use of the miniature pig in toxicology research programs is discussed.
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- 1976
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21. Parkinson's disease is characterized by vitamin B6-dependent inflammatory kynurenine pathway dysfunction.
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Wilson E, Umans J, Swarovski M, Minhas P, Midttun Ø, Ulvik AA, Shahid-Besanti M, Linortner P, Mhatre S, Wang Q, Channappa D, Corso N, Tian L, Fredericks C, Kerchner G, Plowey E, Cholerton B, Ueland P, Zabetian C, Gray N, Quinn J, Montine T, Sha S, Longo F, Wolk D, Chen-Plotkin A, Henderson V, Wyss-Coray T, Wagner A, Mormino E, Aghaeepour N, Poston K, and Andreasson K
- Abstract
Parkinson's disease (PD) is a complex multisystem disorder clinically characterized by motor, non-motor, and premotor manifestations. Pathologically, PD involves neuronal loss in the substantia nigra, striatal dopamine deficiency, and accumulation of intracellular inclusions containing aggregates of α-synuclein. Recent studies demonstrate that PD is associated with dysregulated metabolic flux through the kynurenine pathway (KP), in which tryptophan is converted to kynurenine (KYN), and KYN is subsequently metabolized to neuroactive compounds quinolinic acid (QA) and kynurenic acid (KA). This multicenter study used highly sensitive liquid chromatography-tandem mass-spectrometry to compare blood and cerebral spinal fluid (CSF) KP metabolites between 158 unimpaired older adults and 177 participants with PD. Results indicate that increased neuroexcitatory QA/KA ratio in both plasma and CSF of PD participants associated with peripheral and cerebral inflammation and vitamin B6 deficiency. Furthermore, increased QA tracked with CSF tau and severity of both motor and non-motor PD clinical dysfunction. Importantly, plasma and CSF kynurenine metabolites classified PD participants with a high degree of accuracy (AUC = 0.897). Finally, analysis of metabolite data revealed subgroups with distinct KP profiles, and these were subsequently found to display distinct PD clinical features. Together, these data further support the hypothesis that the KP serves as a site of brain and periphery crosstalk, integrating B-vitamin status, inflammation and metabolism to ultimately influence PD clinical manifestation., Competing Interests: Competing interests: The authors declare that they have no competing interests.
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- 2024
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22. The National Institute on Aging and the Alzheimer's Association Research Framework for Alzheimer's disease: Perspectives from the Research Roundtable.
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Knopman DS, Haeberlein SB, Carrillo MC, Hendrix JA, Kerchner G, Margolin R, Maruff P, Miller DS, Tong G, Tome MB, Murray ME, Nelson PT, Sano M, Mattsson N, Sultzer DL, Montine TJ, Jack CR Jr, Kolb H, Petersen RC, Vemuri P, Canniere MZ, Schneider JA, Resnick SM, Romano G, van Harten AC, Wolk DA, Bain LJ, and Siemers E
- Subjects
- Alzheimer Disease physiopathology, Biomarkers metabolism, Drug Development, Humans, National Institute on Aging (U.S.), United States, Alzheimer Disease diagnosis, Alzheimer Disease therapy, Clinical Trials as Topic
- Abstract
The Alzheimer's Association's Research Roundtable met in November 2017 to explore the new National Institute on Aging and the Alzheimer's Association Research Framework for Alzheimer's disease. The meeting allowed experts in the field from academia, industry, and government to provide perspectives on the new National Institute on Aging and the Alzheimer's Association Research Framework. This review will summarize the "A, T, N System" (Amyloid, Tau, and Neurodegeneration) using biomarkers and how this may be applied to clinical research and drug development. In addition, challenges and barriers to the potential adoption of this new framework will be discussed. Finally, future directions for research will be proposed., (Copyright © 2018 the Alzheimer's Association. Published by Elsevier Inc. All rights reserved.)
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- 2018
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23. A 44-year-old man with profound behavioural changes.
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Laforce R Jr, Kerchner GA, Rabinovici GD, Fong JC, Miller BL, Seeley WW, and Grinberg LT
- Subjects
- Adult, Brain metabolism, Brain pathology, DNA-Binding Proteins metabolism, Electroencephalography, Electromyography, Humans, Magnetic Resonance Imaging, Male, Frontotemporal Lobar Degeneration complications, Frontotemporal Lobar Degeneration diagnosis, Frontotemporal Lobar Degeneration metabolism, RNA-Binding Protein FUS metabolism
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- 2012
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24. Direct presynaptic regulation of GABA/glycine release by kainate receptors in the dorsal horn: an ionotropic mechanism.
- Author
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Kerchner GA, Wang GD, Qiu CS, Huettner JE, and Zhuo M
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- Action Potentials drug effects, Action Potentials physiology, Animals, Cells, Cultured, Dose-Response Relationship, Drug, Excitatory Amino Acid Agonists pharmacology, Ion Channel Gating drug effects, Ion Channel Gating physiology, Kainic Acid pharmacology, Male, Posterior Horn Cells drug effects, Presynaptic Terminals drug effects, Rats, Sensory Receptor Cells drug effects, Sensory Receptor Cells metabolism, Glycine metabolism, Posterior Horn Cells metabolism, Presynaptic Terminals metabolism, Receptors, Kainic Acid physiology, gamma-Aminobutyric Acid metabolism
- Abstract
In the spinal cord dorsal horn, excitatory sensory fibers terminate adjacent to interneuron terminals. Here, we show that kainate (KA) receptor activation triggered action potential-independent release of GABA and glycine from dorsal horn interneurons. This release was transient, because KA receptors desensitized, and it required Na+ entry and Ca2+ channel activation. KA modulated evoked inhibitory transmission in a dose-dependent, biphasic manner, with suppression being more prominent. In recordings from isolated neuron pairs, this suppression required GABA(B) receptor activation, suggesting that KA-triggered GABA release activated presynaptic GABA(B) autoreceptors. Finally, glutamate released from sensory fibers caused a KA and GABA(B) receptor-dependent suppression of inhibitory transmission in spinal slices. Thus, we show how presynaptic KA receptors are linked to changes in GABA/glycine release and highlight a novel role for these receptors in regulating sensory transmission.
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- 2001
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25. Genetic enhancement of inflammatory pain by forebrain NR2B overexpression.
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Wei F, Wang GD, Kerchner GA, Kim SJ, Xu HM, Chen ZF, and Zhuo M
- Subjects
- Animals, Formaldehyde pharmacology, Freund's Adjuvant pharmacology, Hindlimb, Injections, Male, Mice, Mice, Transgenic genetics, Pain Threshold drug effects, Pain Threshold physiology, Receptors, N-Methyl-D-Aspartate genetics, Reference Values, Synapses physiology, Encephalitis physiopathology, Pain physiopathology, Prosencephalon metabolism, Receptors, N-Methyl-D-Aspartate metabolism
- Abstract
N-methyl-D-aspartate (NMDA) receptors contribute to many brain functions. We studied the effect of forebrain-targeted overexpression of the NMDA receptor subunit NR2B on the response of mice to tissue injury and inflammation. Transgenic mice exhibited prominent NR2B expression and enhanced NMDA receptor-mediated synaptic responses in two pain-related forebrain areas, the anterior cingulate cortex and insular cortex, but not in the spinal cord. Although transgenic and wild type mice were indistinguishable in tests of acute pain, transgenic mice exhibited enhanced responsiveness to peripheral injection of two inflammatory stimuli, formalin and complete Freund's adjuvant. Genetic modification of forebrain NMDA receptors can therefore influence pain perception, which suggests that forebrain-selective NMDA receptor antagonists, including NR2B-selective agents, may be useful analgesics for persistent pain.
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- 2001
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26. Presynaptic kainate receptors regulate spinal sensory transmission.
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Kerchner GA, Wilding TJ, Li P, Zhuo M, and Huettner JE
- Subjects
- Animals, Cells, Cultured, Cholinergic Antagonists pharmacology, Coculture Techniques, Dose-Response Relationship, Drug, Excitatory Amino Acid Agonists pharmacology, Excitatory Amino Acid Antagonists pharmacology, Excitatory Postsynaptic Potentials drug effects, GABA-B Receptor Antagonists, Ganglia, Spinal cytology, Ganglia, Spinal drug effects, Ganglia, Spinal metabolism, Glutamic Acid metabolism, Kainic Acid metabolism, Kainic Acid pharmacology, Narcotic Antagonists, Neurons, Afferent cytology, Neurons, Afferent drug effects, Patch-Clamp Techniques, Posterior Horn Cells cytology, Posterior Horn Cells drug effects, Purinergic P1 Receptor Antagonists, Rats, Receptors, AMPA antagonists & inhibitors, Receptors, Kainic Acid agonists, Receptors, Kainic Acid antagonists & inhibitors, Receptors, Metabotropic Glutamate antagonists & inhibitors, Spinal Cord cytology, Spinal Cord drug effects, Spinal Cord metabolism, Synaptic Transmission drug effects, Neurons, Afferent metabolism, Posterior Horn Cells metabolism, Presynaptic Terminals metabolism, Receptors, Kainic Acid metabolism, Synaptic Transmission physiology
- Abstract
Small diameter dorsal root ganglion (DRG) neurons, which include cells that transmit nociceptive information into the spinal cord, are known to express functional kainate receptors. It is well established that exposure to kainate will depolarize C-fiber afferents arising from these cells. Although the role of kainate receptors on sensory afferents is unknown, it has been hypothesized that presynaptic kainate receptors may regulate glutamate release in the spinal cord. Here we show that kainate, applied at low micromolar concentrations in the presence of the AMPA-selective antagonist (RS)-4-(4-aminophenyl)-1, 2-dihydro-1-methyl-2-propyl-carbamoyl-6,7-methylenedioxyphthalazine++ +, suppressed spontaneous NMDA receptor-mediated EPSCs in cultures of spinal dorsal horn neurons. In addition, kainate suppressed EPSCs in dorsal horn neurons evoked by stimulation of synaptically coupled DRG cells in DRG-dorsal horn neuron cocultures. Interestingly, although the glutamate receptor subunit 5-selective kainate receptor agonist (RS)-2-alpha-amino-3-(3-hydroxy-5-tert-butylisoxazol-4-yl) propanoic acid (ATPA) (2 micrometer) was able to suppress DRG-dorsal horn synaptic transmission to a similar extent as kainate (10 micrometer), it had no effect on excitatory transmission between dorsal horn neurons. Agonist applications revealed a striking difference between kainate receptors expressed by DRG and dorsal horn neurons. Whereas DRG cell kainate receptors were sensitive to both kainate and ATPA, most dorsal horn neurons responded only to kainate. Finally, in recordings from dorsal horn neurons in spinal slices, kainate and ATPA were able to suppress NMDA and AMPA receptor-mediated EPSCs evoked by dorsal root fiber stimulation. Together, these data suggest that kainate receptor agonists, acting at a presynaptic locus, can reduce glutamate release from primary afferent sensory synapses.
- Published
- 2001
27. Zn2+ current is mediated by voltage-gated Ca2+ channels and enhanced by extracellular acidity in mouse cortical neurones.
- Author
-
Kerchner GA, Canzoniero LM, Yu SP, Ling C, and Choi DW
- Subjects
- Acids pharmacology, Animals, Calcium metabolism, Calcium Channel Blockers pharmacology, Cell Membrane Permeability drug effects, Cells, Cultured, Cerebral Cortex cytology, Cerebral Cortex metabolism, Dose-Response Relationship, Drug, Extracellular Space drug effects, Fluorescent Dyes, Hydrogen-Ion Concentration drug effects, Ion Transport drug effects, Mice, Neurons cytology, Patch-Clamp Techniques, Zinc pharmacology, Acids metabolism, Calcium Channels metabolism, Extracellular Space metabolism, Neurons metabolism, Zinc metabolism
- Abstract
1. Mammalian neuronal voltage-gated Ca2+ channels have been implicated as potential mediators of membrane permeability to Zn2+. We tested directly whether voltage-gated Ca2+ channels can flux Zn2+ in whole-cell voltage-clamp recordings from cultured murine cortical neurones. 2. In the presence of extracellular Zn2+ and no Na+, K+, or other divalent cations, a small, non-inactivating, voltage-gated inward current was observed exhibiting a current-voltage relationship characteristic of high-voltage activated (HVA) Ca2+ channels. Inward current was detectable at Zn2+ levels as low as 50 microM, and both the amplitude and voltage sensitivity of the current depended upon Zn2+ concentration. This Zn2+ current was sensitive to blockade by Gd3+ and nimodipine and, to a lesser extent, by omega-conotoxin GVIA. 3. Zn2+ could permeate Ca2+ channels in the presence of Ca2+ and other physiological cations. Inward currents recorded with 2 mM Ca2+ were attenuated by Zn2+ (IC50 = 210 microM), and currents recorded with Zn2+ were unaffected by up to equimolar Ca2+ concentrations. Furthermore, the Zn2+-selective fluorescent dye Newport Green revealed a depolarisation-activated, nimodipine-sensitive Zn2+ influx into cortical neurones that were bathed in a physiological extracellular solution plus 300 microM ZnCl2. 4. Surprisingly, while lowering extracellular pH suppressed HVA Ca2+ currents, Zn2+ current amplitude was affected oppositely, varying inversely with pH with an apparent pK of 7.4. The acidity-induced enhancement of Zn2+ current was associated with a positive shift in reversal potential but no change in the kinetics or voltage sensitivity of channel activation. 5. These results provide evidence that L- and N-type voltage-gated Ca2+ channels can mediate Zn2+ entry into cortical neurones and that this entry may be enhanced by extracellular acidity.
- Published
- 2000
- Full Text
- View/download PDF
28. Zinc-induced neuronal death in cortical neurons.
- Author
-
Lobner D, Canzoniero LM, Manzerra P, Gottron F, Ying H, Knudson M, Tian M, Dugan LL, Kerchner GA, Sheline CT, Korsmeyer SJ, and Choi DW
- Subjects
- 2-Amino-5-phosphonovalerate pharmacology, Alleles, Animals, Cell Membrane drug effects, Chromatin metabolism, Cysteine Proteinase Inhibitors pharmacology, DNA Fragmentation drug effects, Dose-Response Relationship, Drug, Electrophoresis, Agar Gel, Excitatory Amino Acid Antagonists pharmacology, Genotype, L-Lactate Dehydrogenase metabolism, Mice, Microscopy, Confocal, Microscopy, Electron, Neuroglia drug effects, Neurons cytology, Neurons ultrastructure, Oligopeptides pharmacology, Proto-Oncogene Proteins genetics, bcl-2-Associated X Protein, Apoptosis drug effects, Necrosis, Neurons metabolism, Neurons pathology, Proto-Oncogene Proteins c-bcl-2, Zinc pharmacology
- Abstract
Although Zn2+ is normally stored and released in the brain, excessive exposure to extracellular Zn2+ can be neurotoxic. The purpose of the present study was to determine the type of neuronal cell death, necrosis versus apoptosis, induced by Zn2+ exposure. Addition of 10-50 microM ZnCl2 to the bathing medium of murine neuronal and glial cell cultures induced, over the next 24 hrs., Zn2+-concentration-dependent neuronal death; some glial death also occurred with Zn2+ concentrations above 30 microM. The neuronal death induced by 20 microM Zn2+ was characterized by coarse chromatin condensation, the formation of apoptotic bodies, and internucleosomal DNA fragmentation. It was attenuated in cortical cell cultures prepared from mice null for the bax gene, and by the caspase inhibitor, benzyloxycarbonyl-Val-Ala-Asp-CH2F (ZVAD, 100 microM), but not by the NMDA receptor antagonist, D-2-amino-5-phosphonovalerate (D-APV, 200 microM ). In contrast, the neuronal death induced by 50 microM Zn2+ was characterized by plasma membrane disruption and random DNA fragmentation; this death was attenuated by D-APV, but exhibited little sensitivity to ZVAD or deletion of bax. These results suggest that Zn2+ can induce cell death with characteristics of either apoptosis or necrosis, depending on the intensity of the Zn2+ exposure.
- Published
- 2000
29. AMPA receptor-PDZ interactions in facilitation of spinal sensory synapses.
- Author
-
Li P, Kerchner GA, Sala C, Wei F, Huettner JE, Sheng M, and Zhuo M
- Subjects
- Animals, Cells, Cultured, Enzyme Activation, In Vitro Techniques, Neurons, Afferent ultrastructure, Protein Kinase C metabolism, Rats, Serotonin pharmacology, Spinal Cord ultrastructure, Neurons, Afferent physiology, Protein Structure, Tertiary, Receptors, AMPA physiology, Spinal Cord physiology, Synapses physiology
- Abstract
Silent synapses form between some primary sensory afferents and dorsal horn neurons in the spinal cord. Molecular mechanisms for activation or conversion of silent synapses to conducting synapses are unknown. Serotonin can trigger activation of silent synapses in dorsal horn neurons by recruiting AMPA receptors. AMPA-receptor subunits GluR2 and GluR3 interact via their cytoplasmic C termini with PDZ-domain-containing proteins such as GRIP (glutamate receptor interacting protein), but the functional significance of these interactions is unclear. Here we demonstrate that protein interactions involving the GluR2/3 C terminus are important for serotonin-induced activation of silent synapses in the spinal cord. Furthermore, PKC is a necessary and sufficient trigger for this activation. These results implicate AMPA receptor-PDZ interactions in mechanisms underlying sensory synaptic potentiation and provide insights into the pathogenesis of chronic pain.
- Published
- 1999
- Full Text
- View/download PDF
30. Genetic enhancement of learning and memory in mice.
- Author
-
Tang YP, Shimizu E, Dube GR, Rampon C, Kerchner GA, Zhuo M, Liu G, and Tsien JZ
- Subjects
- Animals, Association Learning physiology, Cells, Cultured, Conditioning, Classical, Cues, Electric Stimulation, Excitatory Postsynaptic Potentials, Fear physiology, Glutamic Acid physiology, Hippocampus physiology, In Vitro Techniques, Long-Term Potentiation, Maze Learning physiology, Mice, Mice, Inbred C57BL, Mice, Transgenic, Neuronal Plasticity, Prosencephalon physiology, Receptors, AMPA physiology, Receptors, N-Methyl-D-Aspartate genetics, Synapses physiology, Visual Perception physiology, Learning, Memory, Receptors, N-Methyl-D-Aspartate physiology
- Abstract
Hebb's rule (1949) states that learning and memory are based on modifications of synaptic strength among neurons that are simultaneously active. This implies that enhanced synaptic coincidence detection would lead to better learning and memory. If the NMDA (N-methyl-D-aspartate) receptor, a synaptic coincidence detector, acts as a graded switch for memory formation, enhanced signal detection by NMDA receptors should enhance learning and memory. Here we show that overexpression of NMDA receptor 2B (NR2B) in the forebrains of transgenic mice leads to enhanced activation of NMDA receptors, facilitating synaptic potentiation in response to stimulation at 10-100 Hz. These mice exhibit superior ability in learning and memory in various behavioural tasks, showing that NR2B is critical in gating the age-dependent threshold for plasticity and memory formation. NMDA-receptor-dependent modifications of synaptic efficacy, therefore, represent a unifying mechanism for associative learning and memory. Our results suggest that genetic enhancement of mental and cognitive attributes such as intelligence and memory in mammals is feasible.
- Published
- 1999
- Full Text
- View/download PDF
31. Speaking out of turn: a role for silent synapses in pain.
- Author
-
Kerchner GA, Li P, and Zhuo M
- Subjects
- Animals, Humans, Neuronal Plasticity, Spinal Cord physiology, Pain, Receptors, AMPA physiology, Receptors, N-Methyl-D-Aspartate physiology, Synapses physiology, Synaptic Transmission physiology
- Abstract
Severe tissue or nerve injury can result in a chronic and inappropriate sensation of pain, mediated in part by the sensitization of spinal dorsal horn neurons to input from primary afferent fibers. Synaptic transmission at primary afferent synapses is mainly glutamatergic. Although a functioning excitatory synapse contains both alpha-amino-3-hydroxy-5-methyl-4-isoxazoleproprionic acid (AMPA) and N-methyl-D-aspartate (NMDA) receptors in the postsynaptic membrane, recent evidence suggests that dorsal horn neurons contain some "silent" synapses, which exhibit purely NMDA receptor-mediated evoked postsynaptic currents and do not conduct signals at resting membrane potential. Serotonin, which is released onto dorsal horn neurons by descending fibers from the rostroventral medulla, potentiates sensory transmission by activating silent synapses on those neurons, i.e., by recruiting functional AMPA receptors to the postsynaptic membrane. This phenomenon may contribute to the hyperexcitability of dorsal horn neurons seen in chronic pain conditions.
- Published
- 1999
- Full Text
- View/download PDF
32. Endogenous voltage-gated potassium channels in human embryonic kidney (HEK293) cells.
- Author
-
Yu SP and Kerchner GA
- Subjects
- 4-Aminopyridine pharmacology, Animals, CHO Cells metabolism, Cell Line, Cricetinae, Delayed Rectifier Potassium Channels, Electrophysiology, Humans, Kidney cytology, Kidney embryology, Patch-Clamp Techniques, Potassium Channels drug effects, Potassium Channels metabolism, Tetraethylammonium pharmacology, Ion Channel Gating physiology, Kidney metabolism, Potassium Channels physiology, Potassium Channels, Voltage-Gated
- Abstract
Endogenous voltage-gated potassium currents were investigated in human embryonic kidney (HEK293) and Chinese hamster ovary (CHO) cells using whole-cell voltage clamp recording. Depolarizing voltage steps from -70 mV triggered an outwardly rectified current in nontransfected HEK293 cells. This current had an amplitude of 296 pA at +40 mV and a current density of 19.2 pA/pF. The outward current was eliminated by replacing internal K+ with Cs+ and suppressed by the K+ channel blockers tetraethylammonium and 4-aminopyridine. Raising external K+ attenuated the outward current and shifted the reversal potential towards positive potentials as predicted by the Nernst equation. The current had a fast activation phase but inactivated slowly. These features implicate delayed rectifier (I(K))-like channels as mediators of the observed current, which was comparable in size to I(K) currents in many other cells. A small native inward rectifier current but no transient outward current I(A), the M current I(M), or Ca2+-dependent K+ currents were detected in HEK293 cells. In contrast to these findings in HEK293 cells, little or no I(K)-like current was detected in CHO cells. The difference in endogenous voltage-activated currents in HEK293 and CHO cells suggest that CHO cell lines are a preferred system for exogenous K+ channel expression.
- Published
- 1998
- Full Text
- View/download PDF
33. Measurement of intracellular free zinc in living cortical neurons: routes of entry.
- Author
-
Sensi SL, Canzoniero LM, Yu SP, Ying HS, Koh JY, Kerchner GA, and Choi DW
- Subjects
- Animals, Binding, Competitive physiology, Biological Transport physiology, Calcimycin analogs & derivatives, Calcimycin pharmacology, Calcium metabolism, Calcium pharmacology, Calcium Channel Blockers pharmacology, Calcium Channels physiology, Cells, Cultured, Electric Stimulation, Electrophysiology, Excitatory Amino Acid Agonists pharmacology, Excitatory Amino Acid Antagonists pharmacology, Fluorescent Dyes, Fura-2 analogs & derivatives, Ionophores pharmacology, Kainic Acid pharmacology, Magnesium metabolism, Magnesium pharmacology, Membrane Potentials drug effects, Membrane Potentials physiology, Mice, N-Methylaspartate pharmacology, Neocortex cytology, Neurons cytology, Nimodipine pharmacology, Quinoxalines pharmacology, Sodium-Calcium Exchanger metabolism, alpha-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic Acid pharmacology, Neurons chemistry, Neurons metabolism, Zinc analysis, Zinc metabolism
- Abstract
We used the ratioable fluorescent dye mag-fura-5 to measure intracellular free Zn2+ ([Zn2+]i) in cultured neocortical neurons exposed to neurotoxic concentrations of Zn2+ in concert with depolarization or glutamate receptor activation and identified four routes of Zn2+ entry. Neurons exposed to extracellular Zn2+ plus high K+ responded with a peak cell body signal corresponding to a [Zn2+]i of 35-45 nM. This increase in [Zn2+]i was attenuated by concurrent addition of Gd3+, verapamil, omega-conotoxin GVIA, or nimodipine, consistent with Zn2+ entry through voltage-gated Ca2+channels. Furthermore, under conditions favoring reverse operation of the Na+-Ca2+ exchanger, Zn2+ application induced a slow increase in [Zn2+]i and outward whole-cell current sensitive to benzamil-amiloride. Thus, a second route of Zn2+ entry into neurons may be via transporter-mediated exchange with intracellular Na+. Both NMDA and kainate also induced rapid increases in neuronal [Zn2+]i. The NMDA-induced increase was only partly sensitive to Gd3+ or to removal of extracellular Na+, consistent with a third route of entry directly through NMDA receptor-gated channels. The kainate-induced increase was highly sensitive to Gd3+ or Na+ removal in most neurons but insensitive in a minority subpopulation ("cobalt-positive cells"), suggesting that a fourth route of neuronal Zn2+ entry is through the Ca2+-permeable channels gated by certain subtypes of AMPA or kainate receptors.
- Published
- 1997
34. Phencyclidine receptors in rat brain cortex.
- Author
-
Mendelsohn LG, Kerchner GA, Kalra V, Zimmerman DM, and Leander JD
- Subjects
- Animals, Binding, Competitive, Catalepsy physiopathology, Cell Membrane metabolism, Columbidae, Humans, Hydrogen-Ion Concentration, Kinetics, Male, Phencyclidine toxicity, Rats, Rats, Inbred Strains, Receptors, Phencyclidine, Cerebral Cortex metabolism, Phencyclidine metabolism, Receptors, Neurotransmitter metabolism
- Abstract
The binding of [3H]phencyclidine (PCP) to receptors in rat brain cortex has been studied. Two receptors have been detected, a high affinity receptor site with a KD of 23.5 +/- 7.4 nM and a low affinity site with a KD of 7.6 +/- 1.8 microM. The binding of [3H]PCP to its receptors was pH and temperature dependent and was destroyed by heat-denaturation. The binding of [3H]PCP was inhibited by compounds which produce PCP-like behavioral effects including dexoxadrol, etoxadrol and ketamine as well as a novel series of benz(f)isoquinolines. The low affinity site was blocked by PCP, etoxadrol and (+)-SKF-10,047 but not morphine or leu-enkephalin, suggesting that it also represents a specific PCP site. Stereoselective displacement of PCP at the high affinity receptor was observed with the isomers of cyclazocine, cyclorphan, SKF-10,047 and dioxadrol (dexoxadrol and levoxadrol). Naloxone, 4,5,6,7-tetrahydroisoxazolo(S,4-C)pyridin-3-ol (THIP) hydrate and haloperidol inhibited binding poorly (Ki greater than 1 microM), suggesting that these compounds do not interact significantly with the high affinity PCP receptor in vivo. The affinity of ligands for the phencyclidine receptor was highly correlated (r = 0.714, P less than 0.01) with their potency to produce catalepsy in pigeons.
- Published
- 1984
- Full Text
- View/download PDF
35. Autoradiographic localization of insulin-like growth factor II receptors in cerebellar cortex of weaver and Purkinje cell degeneration mutant mice.
- Author
-
Mendelsohn LG, Smith MC, Lucaites VL, Kerchner GA, and Ghetti B
- Subjects
- Animals, Autoradiography, Iodine Radioisotopes, Mice, Receptors, Somatomedin, Reference Values, Species Specificity, Cerebellar Cortex metabolism, Insulin-Like Growth Factor II metabolism, Mice, Neurologic Mutants metabolism, Nerve Degeneration, Purkinje Cells metabolism, Receptors, Cell Surface metabolism, Somatomedins metabolism
- Abstract
Autoradiography was used to visualize insulin-like growth factor II (IGF-II) receptors in the cerebellar cortex of weaver and Purkinje cell degeneration (pcd) mice. These mutants were selected for their respective absence of granule or Purkinje cells. Histological preparations confirmed a severe loss of granule cells in the cerebella of weaver mutants and an absence of Purkinje cells in those of pcd mutants. Autoradiographs showed specific IGF-II binding to the granule cell layer of the cerebellar cortex in control mice, and in pcd mutants. No specific [125I]human IGF-II binding was observed in the cerebellar cortex of weaver mutants. These studies suggest that specific IGF-II receptor sites are located on the granule cells of the cerebellum.
- Published
- 1988
- Full Text
- View/download PDF
36. Nasal delivery of polypeptides I: nasal absorption of enkephalins in rats.
- Author
-
Su KS, Campanale KM, Mendelsohn LG, Kerchner GA, and Gries CL
- Subjects
- Absorption, Administration, Intranasal, Administration, Oral, Animals, Chromatography, High Pressure Liquid, Enkephalin, Leucine analogs & derivatives, Enkephalin, Leucine metabolism, Enkephalin, Leucine-2-Alanine, Enkephalin, Methionine metabolism, Enkephalins administration & dosage, Glycocholic Acid pharmacology, Nasal Mucosa anatomy & histology, Rats, Time Factors, Enkephalins metabolism, Nasal Mucosa metabolism
- Abstract
The serum levels of two enkephalins after various routes of administration were compared in rats. The results indicated that serum levels of metkephamid after nasal administration were not significantly different than levels after intravenous injection. The oral administration of metkephamid resulted in undetectable serum levels. The effects of a promoter and variations in the peptide dose on nasal absorption were studied. Depending on the stability of the polypeptide and its susceptibility to enzymatic degradation, nasal absorption of peptides can be influenced by the presence of a promoting agent in the formulation. A linear relationship between the dose and the AUC was observed in the range of concentrations studied. The absorption mechanism appears to be passive diffusion. Microscopic examinations of nasal mucosa in rats revealed degrees of irritation which, considering the experimental exposure, were slight and probably repairable. The data indicate that enkephalins can be absorbed through the nasal mucosa into the systemic circulation, and the onset of absorption was rapid. Nasal administration may offer an attractive alternative for the delivery of proteins and/or polypeptides which are, in general, absorbed poorly when given orally.
- Published
- 1985
- Full Text
- View/download PDF
37. Studies on the transport of enkephalin-like oligopeptides in rat intestinal mucosa.
- Author
-
Kerchner GA and Geary LE
- Subjects
- Aminopeptidases antagonists & inhibitors, Animals, Biological Transport, Active drug effects, Enkephalin, Leucine metabolism, Enkephalin, Leucine-2-Alanine, Kinetics, Leucine analogs & derivatives, Leucine pharmacology, Male, Puromycin pharmacology, Rats, Rats, Inbred Strains, Enkephalin, Leucine analogs & derivatives, Intestinal Mucosa metabolism, Jejunum metabolism, Oligopeptides metabolism, Tyrosine metabolism
- Abstract
Transport of [D-Ala2, D-Leu5]enkephalin (DADLE(], Tyr-D-Ala-Gly-Phe (TDAGP) and tyrosine into rat jejunum mucosal cells was investigated in vitro. Active transport of either the pentapeptide (DADLE) or the tetrapeptide (TDAGP) into jejunal villi was not detected. Because substantial degradation of these peptides occurred during incubation, the proteolytic enzyme inhibitors, bestatin (30 microM) or D-phenylalanine (20 mM), were added during uptake studies of DADLE or TDAGP, respectively. The presence of these inhibitors significantly reduced degradation of the oligopeptides; however, no accumulation of peptides occurred in the mucosal tissue. Tyrosine was actively transported by the jejunum mucosal cells demonstrating the viability of the transport mechanisms of this in vitro preparation. The results suggest that there are no active transport systems for enkephalin-like oligopeptides.
- Published
- 1983
38. Subacute toxicity of ethylenebisisothiocyanate sulfide in the laboratory rat.
- Author
-
Freudenthal RI, Kerchner GA, Persing RL, Baumel I, and Baron RL
- Subjects
- Animals, Body Weight drug effects, Dermatitis chemically induced, Diet, Dose-Response Relationship, Drug, Iodine Radioisotopes, Isothiocyanates, Methimazole pharmacology, Organ Size drug effects, Rats, Thyroid Function Tests, Thyroxine blood, Triazoles pharmacology, Triiodothyronine blood, Thiocyanates toxicity
- Published
- 1977
- Full Text
- View/download PDF
39. Dietary subacute toxicity of ethylene thiourea in the laboratory rat.
- Author
-
Freudenthal RI, Kerchner G, Persing R, and Baron RL
- Subjects
- Amitrole toxicity, Animals, Body Weight drug effects, Diet, Female, Iodine Radioisotopes, Liver pathology, Male, Propylthiouracil toxicity, Rats, Skin pathology, Thyroid Gland pathology, Thyroid Hormones blood, Time Factors, Ethylenethiourea toxicity, Imidazoles toxicity
- Abstract
Ethylene thiourea (ETU) was fed to groups of rats at 0, 1, 5, 125 or 625 ppm for up to 90 days. Other groups of rats received either propylthiouracil (PTU; 125 ppm) or amitrole (50 ppm) in their diets as positive controls. Only those rats which received ETU at 125 or 625 ppm and those ingesting PTU or amitrole demonstrated a measurable toxic response. This toxicity was reflected as an alteration in thyroid function and a significant change in thyroid morphology. Ingestion of 625 ppm ETU or 125 ppm PTU resulted in very substantial decrease in serum triiodothyronine (T-3) and thyroxine (T-4). Marked increases in serum thyroid stimulating hormone (TSH) levels were found in the 625 and 125 ppm ETU rats, the 125 PTU rats, and the rats receiving amitrole, each time this hormone was measured. Rats which ingested 625 ppm ETU also exhibited a decrease in iodide uptake by the thyroid. While a statistically significant increase in serum T-4 and degree of thyroid hyperplasia was observed for rats ingesting 25 ppm ETU for 60 days, normal thyroid hormone levels and thyroid morphology was found in rats on 25 ppm ETU for either 30 or 90 days. Based on diochemical and microscopic changes examined, the no-effect level for dietary ETU in this 90-day study is considered to be 25 ppm.
- Published
- 1978
40. Immunoregulation by opioid peptides: I. Absence of classical opioid receptor on human mononuclear cells.
- Author
-
Mendelsohn LG, Kerchner GA, Culwell M, and Ades EW
- Subjects
- Enkephalin, Leucine analogs & derivatives, Enkephalin, Leucine blood, Enkephalin, Leucine-2-Alanine, Humans, Kinetics, Ligands, Naloxone blood, B-Lymphocytes metabolism, Monocytes metabolism, Receptors, Opioid metabolism, T-Lymphocytes metabolism
- Abstract
Potent effects of opiates and opioid peptides on the immune responsiveness of mononuclear cells have recently been described. The mechanism by which the effects are mediated was explored by examining the opioid receptor properties of these cells. Human mononuclear cells (B and T lymphocytes and monocytes) were examined for their ability to bind 3H-naloxone, a mu opioid ligand, and 3H-D-Ala2-D-Leu5-enkephalin, a delta opioid ligand. Both ligands bound to nonadherent cells as well as monocytes in a non-specific fashion and could not be competitively displaced by the addition of unlabeled compound. Cells which were stimulated in culture with mitogens did not develop receptors which bound either ligand in a specific fashion. Homogenization of human mononuclear cells prior to measuring binding significantly reduced non-specific binding of radioligands. Although under these conditions a limited amount of net specific binding was observed, this binding was not concentration dependent or saturable and varied considerably between individuals. These observations suggest that opioid effects on immune responsiveness are not mediated through a mononuclear opioid receptor.
- Published
- 1985
41. The insulin-like growth factor-II (IGF-II) receptor of rat brain: regional distribution visualized by autoradiography.
- Author
-
Smith M, Clemens J, Kerchner GA, and Mendelsohn LG
- Subjects
- Animals, Autoradiography, Brain cytology, Iodine Radioisotopes, Male, Organ Specificity, Rats, Rats, Inbred Strains, Receptors, Somatomedin, Brain metabolism, Insulin-Like Growth Factor II metabolism, Receptor, Insulin metabolism, Somatomedins metabolism
- Abstract
The presence of insulin-like growth factor-II (IGF-II) in brain and cerebral spinal fluid prompted us to investigate the distribution of receptors for this peptide in rat brain slices. Human 125I-IGF-II (10 pM) was incubated for 16 h at 4 degrees C with thaw-mounted slices of rat brain from 11 different brain regions. Incubations in the absence or presence of excess unlabeled human IGF-II or insulin were performed and the labeled tissues were exposed to X-ray film for 4-7 days. Autoradiographs showed dense labeling in the granule layers of the olfactory bulbs, deep layers of the cerebral cortex, pineal gland, anterior pituitary, hippocampus (CA1-CA4, and dentate gyrus), and the granule cell layers of the cerebellum. Unlabeled IGF-II eliminated most of the binding in these brain regions while insulin produced only a minimal reduction in the amount of 125I-IGF-II bound. These results indicate that a neural receptor for IGF-II is uniquely distributed in rat brain tissue supporting the notion that this peptide might play an important role in neuronal functioning.
- Published
- 1988
- Full Text
- View/download PDF
42. Comparison of the drug metabolizing enzymes in the liver and kidneys from homozygous nude swiss, heterozygous normal swiss, homozygous normal Swiss and DBA/2 mice.
- Author
-
Freudenthal RI, Leber AP, Emmerling DC, Kerchner GA, and Ovejera AA
- Subjects
- Animals, Body Weight drug effects, Female, Kidney drug effects, Liver drug effects, Mice, Mice, Inbred DBA, Mice, Nude, Organ Size drug effects, Species Specificity, Kidney enzymology, Liver enzymology, Mixed Function Oxygenases metabolism, Oxidoreductases metabolism
- Abstract
The hepatic and renal microsomal drug metabolizing enzyme systems were isolated from homozygous nude Swiss (nu/nu), heterozygous normal Swiss (nu/+), homozygous normal Swiss (+/+) and DBA/2 mice. Microsomal protein and cytochrome P-450 concentrations were measured and the activity of ethylmorphine demethylase, aniline hydroxylase, aryl hydrocarbon hydroxylase and UDP-glucuronyl transferase were determined. Hepatic microsomes from both experimental groups carrying the nude gene were able to metabolize aniline and ethylmorphine more rapidly (20% and 36%, respectively) than the DBA/2 or Swiss homozygous normal mice. No difference between test groups was observed for hepatic aryl hydrocarbon hydroxylase or UDP-glucuronyl transferase activity. Kidney microsomes from mice carrying the nude gene had approximately twice the aryl hydrocarbon hydroxylase activity of the other two experimental groups. Renal mixed-function oxidase pathways measured for the homozygous nude mouse showed a higher overall rate of activity than the other three experimental groups. No significant difference in renal UDP-glucuronyl transferase was observed between mouse groups.
- Published
- 1976
43. Venereal disease control by New York City Health Department in relation to cooperation with the armed forces.
- Author
-
ROSENTHAL T and KERCHNER G
- Subjects
- Humans, New York City, Biomedical Research, Interpersonal Relations, Military Personnel, Sexually Transmitted Diseases prevention & control
- Published
- 1946
44. Experiences with registered letter follow-up in the New York City Health Department.
- Author
-
ROSENTHAL T and KERCHNER G
- Subjects
- Follow-Up Studies, Humans, New York City, Biomedical Research, Sexually Transmitted Diseases prevention & control
- Published
- 1946
45. Venereal disease in prostitutes.
- Author
-
ROSENTHAL T and KERCHNER G
- Subjects
- Humans, Sex Work, Sex Workers, Sexually Transmitted Diseases
- Published
- 1948
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