Search

Your search keyword '"Blennow, K."' showing total 3,382 results
Start Over Author "Blennow, K."
3,382 results on '"Blennow, K."'

12. An interim exploratory biomarker analysis of a Phase 2 clinical trial to assess the impact of CT1812 in Alzheimer’s disease

Author

Lizama, BN, primary, North, HA, additional, Pandey, K, additional, Williams, C, additional, Duong, D, additional, Cho, E, additional, Di Caro, V, additional, Ping, L, additional, Blennow, K, additional, Zetterberg, H, additional, Lah, J, additional, Levey, AI, additional, Grundman, M, additional, Caggiano, AO, additional, Seyfried, NT, additional, and Hamby, ME, additional

Published
2024
Full Text
View/download PDF

13. Author Correction: Common variants in Alzheimer’s disease and risk stratification by polygenic risk scores (Nature Communications, (2021), 12, 1, (3417), 10.1038/s41467-021-22491-8)

Author

de Rojas I., de Rojas, I, Moreno-Grau, S, Tesi, N, Grenier-Boley, B, Andrade, V, Jansen, I, Pedersen, N, Stringa, N, Zettergren, A, Hernandez, I, Montrreal, L, Antunez, C, Antonell, A, Tankard, R, Bis, J, Sims, R, Bellenguez, C, Quintela, I, Gonzalez-Perez, A, Calero, M, Franco-Macias, E, Macias, J, Blesa, R, Cervera-Carles, L, Menendez-Gonzalez, M, Frank-Garcia, A, Royo, J, Moreno, F, Huerto Vilas, R, Baquero, M, Diez-Fairen, M, Lage, C, Garcia-Madrona, S, Garcia-Gonzalez, P, Alarcon-Martin, E, Valero, S, Sotolongo-Grau, O, Ullgren, A, Naj, A, Lemstra, A, Benaque, A, Perez-Cordon, A, Benussi, A, Rabano, A, Padovani, A, Squassina, A, de Mendonca, A, Arias Pastor, A, Kok, A, Meggy, A, Pastor, A, Espinosa, A, Corma-Gomez, A, Martin Montes, A, Sanabria, A, Destefano, A, Schneider, A, Haapasalo, A, Kinhult Stahlbom, A, Tybjaerg-Hansen, A, Hartmann, A, Spottke, A, Corbaton-Anchuelo, A, Rongve, A, Borroni, B, Arosio, B, Nacmias, B, Nordestgaard, B, Kunkle, B, Charbonnier, C, Abdelnour, C, Masullo, C, Martinez Rodriguez, C, Munoz-Fernandez, C, Dufouil, C, Graff, C, Ferreira, C, Chillotti, C, Reynolds, C, Fenoglio, C, Van Broeckhoven, C, Clark, C, Pisanu, C, Satizabal, C, Holmes, C, Buiza-Rueda, D, Aarsland, D, Rujescu, D, Alcolea, D, Galimberti, D, Wallon, D, Seripa, D, Grunblatt, E, Dardiotis, E, Duzel, E, Scarpini, E, Conti, E, Rubino, E, Gelpi, E, Rodriguez-Rodriguez, E, Duron, E, Boerwinkle, E, Ferri, E, Tagliavini, F, Kucukali, F, Pasquier, F, Sanchez-Garcia, F, Mangialasche, F, Jessen, F, Nicolas, G, Selbaek, G, Ortega, G, Chene, G, Hadjigeorgiou, G, Rossi, G, Spalletta, G, Giaccone, G, Grande, G, Binetti, G, Papenberg, G, Hampel, H, Bailly, H, Zetterberg, H, Soininen, H, Karlsson, I, Alvarez, I, Appollonio, I, Giegling, I, Skoog, I, Saltvedt, I, Rainero, I, Rosas Allende, I, Hort, J, Diehl-Schmid, J, Van Dongen, J, Vidal, J, Lehtisalo, J, Wiltfang, J, Thomassen, J, Kornhuber, J, Haines, J, Vogelgsang, J, Pineda, J, Fortea, J, Popp, J, Deckert, J, Buerger, K, Morgan, K, Fliessbach, K, Sleegers, K, Molina-Porcel, L, Kilander, L, Weinhold, L, Farrer, L, Wang, L, Kleineidam, L, Farotti, L, Parnetti, L, Tremolizzo, L, Hausner, L, Benussi, L, Froelich, L, Ikram, M, Deniz-Naranjo, M, Tsolaki, M, Rosende-Roca, M, Lowenmark, M, Hulsman, M, Spallazzi, M, Pericak-Vance, M, Esiri, M, Bernal Sanchez-Arjona, M, Dalmasso, M, Martinez-Larrad, M, Arcaro, M, Nothen, M, Fernandez-Fuertes, M, Dichgans, M, Ingelsson, M, Herrmann, M, Scherer, M, Vyhnalek, M, Kosmidis, M, Yannakoulia, M, Schmid, M, Ewers, M, Heneka, M, Wagner, M, Scamosci, M, Kivipelto, M, Hiltunen, M, Zulaica, M, Alegret, M, Fornage, M, Roberto, N, van Schoor, N, Seidu, N, Banaj, N, Armstrong, N, Scarmeas, N, Scherbaum, N, Goldhardt, O, Hanon, O, Peters, O, Skrobot, O, Quenez, O, Lerch, O, Bossu, P, Caffarra, P, Dionigi Rossi, P, Sakka, P, Mecocci, P, Hoffmann, P, Holmans, P, Fischer, P, Riederer, P, Yang, Q, Marshall, R, Kalaria, R, Mayeux, R, Vandenberghe, R, Cecchetti, R, Ghidoni, R, Frikke-Schmidt, R, Sorbi, S, Hagg, S, Engelborghs, S, Helisalmi, S, Botne Sando, S, Kern, S, Archetti, S, Boschi, S, Fostinelli, S, Gil, S, Mendoza, S, Mead, S, Ciccone, S, Djurovic, S, Heilmann-Heimbach, S, Riedel-Heller, S, Kuulasmaa, T, del Ser, T, Lebouvier, T, Polak, T, Ngandu, T, Grimmer, T, Bessi, V, Escott-Price, V, Giedraitis, V, Deramecourt, V, Maier, W, Jian, X, Pijnenburg, Y, Smith, A, Saenz, A, Bizzarro, A, Lauria, A, Vacca, A, Solomon, A, Anastasiou, A, Richardson, A, Boland, A, Koivisto, A, Daniele, A, Greco, A, Marianthi, A, Mcguinness, B, Fin, B, Ferrari, C, Custodero, C, Ferrarese, C, Ingino, C, Mangone, C, Reyes Toso, C, Martinez, C, Cuesta, C, Muchnik, C, Joachim, C, Ortiz, C, Besse, C, Johansson, C, Zoia, C, Laske, C, Anastasiou, C, Palacio, D, Politis, D, Janowitz, D, Craig, D, Mann, D, Neary, D, Jurgen, D, Daian, D, Belezhanska, D, Kohler, E, Castano, E, Koutsouraki, E, Chipi, E, De Roeck, E, Costantini, E, Vardy, E, Piras, F, Roveta, F, Prestia, F, Assogna, F, Salani, F, Sala, G, Lacidogna, G, Novack, G, Wilcock, G, Thonberg, H, Kolsch, H, Weber, H, Boecker, H, Etchepareborda, I, Piaceri, I, Tuomilehto, J, Lindstrom, J, Laczo, J, Johnston, J, Deleuze, J, Harris, J, Schott, J, Priller, J, Bacha, J, Snowden, J, Lisso, J, Mihova, K, Traykov, L, Morelli, L, Brusco, L, Rainer, M, Takalo, M, Bjerke, M, Del Zompo, M, Serpente, M, Sanchez Abalos, M, Rios, M, Peltonen, M, Herrman, M, Kohler, M, Rojo, M, Jones, M, Orsini, M, Medel, N, Olivar, N, Fox, N, Salvadori, N, Hooper, N, Galeano, P, Solis, P, Bastiani, P, Passmore, P, Heun, R, Antikainen, R, Olaso, R, Perneczky, R, Germani, S, Lopez-Garcia, S, Love, S, Mehrabian, S, Bagnoli, S, Kochen, S, Andreoni, S, Teipel, S, Todd, S, Pickering-Brown, S, Natunen, T, Tegos, T, Laatikainen, T, Strandberg, T, Polvikoski, T, Matoska, V, Ciullo, V, Cores, V, Solfrizzi, V, Lisetti, V, Sevillano, Z, Aguilera, N, Alarcon, E, Boada, M, Buendia, M, Canabate, P, Carracedo, A, Diego, S, Gailhajenet, A, Guitart, M, Ibarria, M, Lafuente, A, Maronas, O, Martin, E, Martinez, M, Marquie, M, Mauleon, A, Moreno, M, Orellana, A, Pancho, A, Peleja, E, Preckler, S, Real, L, Ruiz, A, Saez, M, Serrano-Rios, M, Tarraga, L, Vargas, L, Adarmes-Gomez, A, Alonso, M, Alvarez, V, Amer-Ferrer, G, Antequera, M, Bernal, M, Bullido, M, Burguera, J, Carrillo, F, Carrion-Claro, M, Casajeros, M, Clarimon, J, Cruz-Gamero, J, de Pancorbo, M, Escuela, R, Garrote-Espina, L, Garcia-Alberca, J, Garcia Madrona, S, Garcia-Ribas, G, Gomez-Garre, P, Hevilla, S, Jesus, S, Labrador Espinosa, M, Legaz, A, Lleo, A, Lopez de Munain, A, Macias-Garcia, D, Manzanares, S, Marin, M, Marin-Munoz, J, Marin, T, Martinez, B, Martinez, V, Martinez-Lage Alvarez, P, Medina, M, Mendioroz Iriarte, M, Mir, P, Molinuevo, J, Pastor, P, Perez Tur, J, Perinan-Tocino, T, Pineda-Sanchez, R, Pinol-Ripoll, G, Real de Asua, D, Rodrigo, S, Sanchez del Valle Diaz, R, Sanchez-Juan, P, Sastre, I, Vicente, M, Vigo-Ortega, R, Vivancos, L, Macleod, C, Mccracken, C, Brayne, C, Bresner, C, Grozeva, D, Bellou, E, Sommerville, E, Matthews, F, Leonenko, G, Menzies, G, Windle, G, Harwood, J, Phillips, J, Bennett, K, Luckuck, L, Clare, L, Woods, R, Saad, S, Burholt, V, Kehoe, P, Scheltens, P, Holstege, H, Amouyel, P, Schellenberg, G, Williams, J, Seshadri, S, van Duijn, C, Mather, K, Sanchez-Valle, R, Blennow, K, Huisman, M, Andreassen, O, Posthuma, D, van der Flier, W, Ramirez, A, Lambert, J, van der Lee, S, de Rojas I., Moreno-Grau S., Tesi N., Grenier-Boley B., Andrade V., Jansen I. E., Pedersen N. L., Stringa N., Zettergren A., Hernandez I., Montrreal L., Antunez C., Antonell A., Tankard R. M., Bis J. C., Sims R., Bellenguez C., Quintela I., Gonzalez-Perez A., Calero M., Franco-Macias E., Macias J., Blesa R., Cervera-Carles L., Menendez-Gonzalez M., Frank-Garcia A., Royo J. L., Moreno F., Huerto Vilas R., Baquero M., Diez-Fairen M., Lage C., Garcia-Madrona S., Garcia-Gonzalez P., Alarcon-Martin E., Valero S., Sotolongo-Grau O., Ullgren A., Naj A. C., Lemstra A. W., Benaque A., Perez-Cordon A., Benussi A., Rabano A., Padovani A., Squassina A., de Mendonca A., Arias Pastor A., Kok A. A. L., Meggy A., Pastor A. B., Espinosa A., Corma-Gomez A., Martin Montes A., Sanabria A., DeStefano A. L., Schneider A., Haapasalo A., Kinhult Stahlbom A., Tybjaerg-Hansen A., Hartmann A. M., Spottke A., Corbaton-Anchuelo A., Rongve A., Borroni B., Arosio B., Nacmias B., Nordestgaard B. G., Kunkle B. W., Charbonnier C., Abdelnour C., Masullo C., Martinez Rodriguez C., Munoz-Fernandez C., Dufouil C., Graff C., Ferreira C. B., Chillotti C., Reynolds C. A., Fenoglio C., Van Broeckhoven C., Clark C., Pisanu C., Satizabal C. L., Holmes C., Buiza-Rueda D., Aarsland D., Rujescu D., Alcolea D., Galimberti D., Wallon D., Seripa D., Grunblatt E., Dardiotis E., Duzel E., Scarpini E., Conti E., Rubino E., Gelpi E., Rodriguez-Rodriguez E., Duron E., Boerwinkle E., Ferri E., Tagliavini F., Kucukali F., Pasquier F., Sanchez-Garcia F., Mangialasche F., Jessen F., Nicolas G., Selbaek G., Ortega G., Chene G., Hadjigeorgiou G., Rossi G., Spalletta G., Giaccone G., Grande G., Binetti G., Papenberg G., Hampel H., Bailly H., Zetterberg H., Soininen H., Karlsson I. K., Alvarez I., Appollonio I., Giegling I., Skoog I., Saltvedt I., Rainero I., Rosas Allende I., Hort J., Diehl-Schmid J., Van Dongen J., Vidal J. -S., Lehtisalo J., Wiltfang J., Thomassen J. Q., Kornhuber J., Haines J. L., Vogelgsang J., Pineda J. A., Fortea J., Popp J., Deckert J., Buerger K., Morgan K., Fliessbach K., Sleegers K., Molina-Porcel L., Kilander L., Weinhold L., Farrer L. A., Wang L. -S., Kleineidam L., Farotti L., Parnetti L., Tremolizzo L., Hausner L., Benussi L., Froelich L., Ikram M. A., Deniz-Naranjo M. C., Tsolaki M., Rosende-Roca M., Lowenmark M., Hulsman M., Spallazzi M., Pericak-Vance M. A., Esiri M., Bernal Sanchez-Arjona M., Dalmasso M. C., Martinez-Larrad M. T., Arcaro M., Nothen M. M., Fernandez-Fuertes M., Dichgans M., Ingelsson M., Herrmann M. J., Scherer M., Vyhnalek M., Kosmidis M. H., Yannakoulia M., Schmid M., Ewers M., Heneka M. T., Wagner M., Scamosci M., Kivipelto M., Hiltunen M., Zulaica M., Alegret M., Fornage M., Roberto N., van Schoor N. M., Seidu N. M., Banaj N., Armstrong N. J., Scarmeas N., Scherbaum N., Goldhardt O., Hanon O., Peters O., Skrobot O. A., Quenez O., Lerch O., Bossu P., Caffarra P., Dionigi Rossi P., Sakka P., Mecocci P., Hoffmann P., Holmans P. A., Fischer P., Riederer P., Yang Q., Marshall R., Kalaria R. N., Mayeux R., Vandenberghe R., Cecchetti R., Ghidoni R., Frikke-Schmidt R., Sorbi S., Hagg S., Engelborghs S., Helisalmi S., Botne Sando S., Kern S., Archetti S., Boschi S., Fostinelli S., Gil S., Mendoza S., Mead S., Ciccone S., Djurovic S., Heilmann-Heimbach S., Riedel-Heller S., Kuulasmaa T., del Ser T., Lebouvier T., Polak T., Ngandu T., Grimmer T., Bessi V., Escott-Price V., Giedraitis V., Deramecourt V., Maier W., Jian X., Pijnenburg Y. A. L., Smith A. D., Saenz A., Bizzarro A., Lauria A., Vacca A., Solomon A., Anastasiou A., Richardson A., Boland A., Koivisto A., Daniele A., Greco A., Marianthi A., McGuinness B., Fin B., Ferrari C., Custodero C., Ferrarese C., Ingino C., Mangone C., Reyes Toso C., Martinez C., Cuesta C., Muchnik C., Joachim C., Ortiz C., Besse C., Johansson C., Zoia C. P., Laske C., Anastasiou C., Palacio D. L., Politis D. G., Janowitz D., Craig D., Mann D. M., Neary D., Jurgen D., Daian D., Belezhanska D., Kohler E., Castano E. M., Koutsouraki E., Chipi E., De Roeck E., Costantini E., Vardy E. R. L. C., Piras F., Roveta F., Prestia F. A., Assogna F., Salani F., Sala G., Lacidogna G., Novack G., Wilcock G., Thonberg H., Kolsch H., Weber H., Boecker H., Etchepareborda I., Piaceri I., Tuomilehto J., Lindstrom J., Laczo J., Johnston J., Deleuze J. -F., Harris J., Schott J. M., Priller J., Bacha J. I., Snowden J., Lisso J., Mihova K. Y., Traykov L., Morelli L., Brusco L. I., Rainer M., Takalo M., Bjerke M., Del Zompo M., Serpente M., Sanchez Abalos M., Rios M., Peltonen M., Herrman M. J., Kohler M., Rojo M., Jones M., Orsini M., Medel N., Olivar N., Fox N. C., Salvadori N., Hooper N. M., Galeano P., Solis P., Bastiani P., Passmore P., Heun R., Antikainen R., Olaso R., Perneczky R., Germani S., Lopez-Garcia S., Love S., Mehrabian S., Bagnoli S., Kochen S., Andreoni S., Teipel S., Todd S., Pickering-Brown S., Natunen T., Tegos T., Laatikainen T., Strandberg T., Polvikoski T. M., Matoska V., Ciullo V., Cores V., Solfrizzi V., Lisetti V., Sevillano Z., Aguilera N., Alarcon E., Boada M., Buendia M., Canabate P., Carracedo A., Diego S., Gailhajenet A., Guitart M., Ibarria M., Lafuente A., Maronas O., Martin E., Martinez M. T., Marquie M., Mauleon A., Moreno M., Orellana A., Pancho A., Peleja E., Preckler S., Real L. M., Ruiz A., Saez M. E., Serrano-Rios M., Tarraga L., Vargas L., Adarmes-Gomez A. D., Alonso M. D., Alvarez V., Amer-Ferrer G., Antequera M., Bernal M., Bullido M. J., Burguera J. A., Carrillo F., Carrion-Claro M., Casajeros M. J., Clarimon J., Cruz-Gamero J. M., de Pancorbo M. M., Escuela R., Garrote-Espina L., Garcia-Alberca J. M., Garcia Madrona S., Garcia-Ribas G., Gomez-Garre P., Hevilla S., Jesus S., Labrador Espinosa M. A., Legaz A., Lleo A., Lopez de Munain A., Macias-Garcia D., Manzanares S., Marin M., Marin-Munoz J., Marin T., Martinez B., Martinez V., Martinez-Lage Alvarez P., Medina M., Mendioroz Iriarte M., Mir P., Molinuevo J. L., Pastor P., Perez Tur J., Perinan-Tocino T., Pineda-Sanchez R., Pinol-Ripoll G., Real de Asua D., Rodrigo S., Sanchez del Valle Diaz R., Sanchez-Juan P., Sastre I., Vicente M. P., Vigo-Ortega R., Vivancos L., Macleod C., McCracken C., Brayne C., Bresner C., Grozeva D., Bellou E., Sommerville E. W., Matthews F., Leonenko G., Menzies G., Windle G., Harwood J., Phillips J., Bennett K., Luckuck L., Clare L., Woods R., Saad S., Burholt V., Kehoe P. G., Scheltens P., Holstege H., Amouyel P., Schellenberg G. D., Williams J., Seshadri S., van Duijn C. M., Mather K. A., Sanchez-Valle R., Blennow K., Huisman M., Andreassen O. A., Posthuma D., van der Flier W. M., Ramirez A., Lambert J. -C., van der Lee S. J., de Rojas I., de Rojas, I, Moreno-Grau, S, Tesi, N, Grenier-Boley, B, Andrade, V, Jansen, I, Pedersen, N, Stringa, N, Zettergren, A, Hernandez, I, Montrreal, L, Antunez, C, Antonell, A, Tankard, R, Bis, J, Sims, R, Bellenguez, C, Quintela, I, Gonzalez-Perez, A, Calero, M, Franco-Macias, E, Macias, J, Blesa, R, Cervera-Carles, L, Menendez-Gonzalez, M, Frank-Garcia, A, Royo, J, Moreno, F, Huerto Vilas, R, Baquero, M, Diez-Fairen, M, Lage, C, Garcia-Madrona, S, Garcia-Gonzalez, P, Alarcon-Martin, E, Valero, S, Sotolongo-Grau, O, Ullgren, A, Naj, A, Lemstra, A, Benaque, A, Perez-Cordon, A, Benussi, A, Rabano, A, Padovani, A, Squassina, A, de Mendonca, A, Arias Pastor, A, Kok, A, Meggy, A, Pastor, A, Espinosa, A, Corma-Gomez, A, Martin Montes, A, Sanabria, A, Destefano, A, Schneider, A, Haapasalo, A, Kinhult Stahlbom, A, Tybjaerg-Hansen, A, Hartmann, A, Spottke, A, Corbaton-Anchuelo, A, Rongve, A, Borroni, B, Arosio, B, Nacmias, B, Nordestgaard, B, Kunkle, B, Charbonnier, C, Abdelnour, C, Masullo, C, Martinez Rodriguez, C, Munoz-Fernandez, C, Dufouil, C, Graff, C, Ferreira, C, Chillotti, C, Reynolds, C, Fenoglio, C, Van Broeckhoven, C, Clark, C, Pisanu, C, Satizabal, C, Holmes, C, Buiza-Rueda, D, Aarsland, D, Rujescu, D, Alcolea, D, Galimberti, D, Wallon, D, Seripa, D, Grunblatt, E, Dardiotis, E, Duzel, E, Scarpini, E, Conti, E, Rubino, E, Gelpi, E, Rodriguez-Rodriguez, E, Duron, E, Boerwinkle, E, Ferri, E, Tagliavini, F, Kucukali, F, Pasquier, F, Sanchez-Garcia, F, Mangialasche, F, Jessen, F, Nicolas, G, Selbaek, G, Ortega, G, Chene, G, Hadjigeorgiou, G, Rossi, G, Spalletta, G, Giaccone, G, Grande, G, Binetti, G, Papenberg, G, Hampel, H, Bailly, H, Zetterberg, H, Soininen, H, Karlsson, I, Alvarez, I, Appollonio, I, Giegling, I, Skoog, I, Saltvedt, I, Rainero, I, Rosas Allende, I, Hort, J, Diehl-Schmid, J, Van Dongen, J, Vidal, J, Lehtisalo, J, Wiltfang, J, Thomassen, J, Kornhuber, J, Haines, J, Vogelgsang, J, Pineda, J, Fortea, J, Popp, J, Deckert, J, Buerger, K, Morgan, K, Fliessbach, K, Sleegers, K, Molina-Porcel, L, Kilander, L, Weinhold, L, Farrer, L, Wang, L, Kleineidam, L, Farotti, L, Parnetti, L, Tremolizzo, L, Hausner, L, Benussi, L, Froelich, L, Ikram, M, Deniz-Naranjo, M, Tsolaki, M, Rosende-Roca, M, Lowenmark, M, Hulsman, M, Spallazzi, M, Pericak-Vance, M, Esiri, M, Bernal Sanchez-Arjona, M, Dalmasso, M, Martinez-Larrad, M, Arcaro, M, Nothen, M, Fernandez-Fuertes, M, Dichgans, M, Ingelsson, M, Herrmann, M, Scherer, M, Vyhnalek, M, Kosmidis, M, Yannakoulia, M, Schmid, M, Ewers, M, Heneka, M, Wagner, M, Scamosci, M, Kivipelto, M, Hiltunen, M, Zulaica, M, Alegret, M, Fornage, M, Roberto, N, van Schoor, N, Seidu, N, Banaj, N, Armstrong, N, Scarmeas, N, Scherbaum, N, Goldhardt, O, Hanon, O, Peters, O, Skrobot, O, Quenez, O, Lerch, O, Bossu, P, Caffarra, P, Dionigi Rossi, P, Sakka, P, Mecocci, P, Hoffmann, P, Holmans, P, Fischer, P, Riederer, P, Yang, Q, Marshall, R, Kalaria, R, Mayeux, R, Vandenberghe, R, Cecchetti, R, Ghidoni, R, Frikke-Schmidt, R, Sorbi, S, Hagg, S, Engelborghs, S, Helisalmi, S, Botne Sando, S, Kern, S, Archetti, S, Boschi, S, Fostinelli, S, Gil, S, Mendoza, S, Mead, S, Ciccone, S, Djurovic, S, Heilmann-Heimbach, S, Riedel-Heller, S, Kuulasmaa, T, del Ser, T, Lebouvier, T, Polak, T, Ngandu, T, Grimmer, T, Bessi, V, Escott-Price, V, Giedraitis, V, Deramecourt, V, Maier, W, Jian, X, Pijnenburg, Y, Smith, A, Saenz, A, Bizzarro, A, Lauria, A, Vacca, A, Solomon, A, Anastasiou, A, Richardson, A, Boland, A, Koivisto, A, Daniele, A, Greco, A, Marianthi, A, Mcguinness, B, Fin, B, Ferrari, C, Custodero, C, Ferrarese, C, Ingino, C, Mangone, C, Reyes Toso, C, Martinez, C, Cuesta, C, Muchnik, C, Joachim, C, Ortiz, C, Besse, C, Johansson, C, Zoia, C, Laske, C, Anastasiou, C, Palacio, D, Politis, D, Janowitz, D, Craig, D, Mann, D, Neary, D, Jurgen, D, Daian, D, Belezhanska, D, Kohler, E, Castano, E, Koutsouraki, E, Chipi, E, De Roeck, E, Costantini, E, Vardy, E, Piras, F, Roveta, F, Prestia, F, Assogna, F, Salani, F, Sala, G, Lacidogna, G, Novack, G, Wilcock, G, Thonberg, H, Kolsch, H, Weber, H, Boecker, H, Etchepareborda, I, Piaceri, I, Tuomilehto, J, Lindstrom, J, Laczo, J, Johnston, J, Deleuze, J, Harris, J, Schott, J, Priller, J, Bacha, J, Snowden, J, Lisso, J, Mihova, K, Traykov, L, Morelli, L, Brusco, L, Rainer, M, Takalo, M, Bjerke, M, Del Zompo, M, Serpente, M, Sanchez Abalos, M, Rios, M, Peltonen, M, Herrman, M, Kohler, M, Rojo, M, Jones, M, Orsini, M, Medel, N, Olivar, N, Fox, N, Salvadori, N, Hooper, N, Galeano, P, Solis, P, Bastiani, P, Passmore, P, Heun, R, Antikainen, R, Olaso, R, Perneczky, R, Germani, S, Lopez-Garcia, S, Love, S, Mehrabian, S, Bagnoli, S, Kochen, S, Andreoni, S, Teipel, S, Todd, S, Pickering-Brown, S, Natunen, T, Tegos, T, Laatikainen, T, Strandberg, T, Polvikoski, T, Matoska, V, Ciullo, V, Cores, V, Solfrizzi, V, Lisetti, V, Sevillano, Z, Aguilera, N, Alarcon, E, Boada, M, Buendia, M, Canabate, P, Carracedo, A, Diego, S, Gailhajenet, A, Guitart, M, Ibarria, M, Lafuente, A, Maronas, O, Martin, E, Martinez, M, Marquie, M, Mauleon, A, Moreno, M, Orellana, A, Pancho, A, Peleja, E, Preckler, S, Real, L, Ruiz, A, Saez, M, Serrano-Rios, M, Tarraga, L, Vargas, L, Adarmes-Gomez, A, Alonso, M, Alvarez, V, Amer-Ferrer, G, Antequera, M, Bernal, M, Bullido, M, Burguera, J, Carrillo, F, Carrion-Claro, M, Casajeros, M, Clarimon, J, Cruz-Gamero, J, de Pancorbo, M, Escuela, R, Garrote-Espina, L, Garcia-Alberca, J, Garcia Madrona, S, Garcia-Ribas, G, Gomez-Garre, P, Hevilla, S, Jesus, S, Labrador Espinosa, M, Legaz, A, Lleo, A, Lopez de Munain, A, Macias-Garcia, D, Manzanares, S, Marin, M, Marin-Munoz, J, Marin, T, Martinez, B, Martinez, V, Martinez-Lage Alvarez, P, Medina, M, Mendioroz Iriarte, M, Mir, P, Molinuevo, J, Pastor, P, Perez Tur, J, Perinan-Tocino, T, Pineda-Sanchez, R, Pinol-Ripoll, G, Real de Asua, D, Rodrigo, S, Sanchez del Valle Diaz, R, Sanchez-Juan, P, Sastre, I, Vicente, M, Vigo-Ortega, R, Vivancos, L, Macleod, C, Mccracken, C, Brayne, C, Bresner, C, Grozeva, D, Bellou, E, Sommerville, E, Matthews, F, Leonenko, G, Menzies, G, Windle, G, Harwood, J, Phillips, J, Bennett, K, Luckuck, L, Clare, L, Woods, R, Saad, S, Burholt, V, Kehoe, P, Scheltens, P, Holstege, H, Amouyel, P, Schellenberg, G, Williams, J, Seshadri, S, van Duijn, C, Mather, K, Sanchez-Valle, R, Blennow, K, Huisman, M, Andreassen, O, Posthuma, D, van der Flier, W, Ramirez, A, Lambert, J, van der Lee, S, de Rojas I., Moreno-Grau S., Tesi N., Grenier-Boley B., Andrade V., Jansen I. E., Pedersen N. L., Stringa N., Zettergren A., Hernandez I., Montrreal L., Antunez C., Antonell A., Tankard R. M., Bis J. C., Sims R., Bellenguez C., Quintela I., Gonzalez-Perez A., Calero M., Franco-Macias E., Macias J., Blesa R., Cervera-Carles L., Menendez-Gonzalez M., Frank-Garcia A., Royo J. L., Moreno F., Huerto Vilas R., Baquero M., Diez-Fairen M., Lage C., Garcia-Madrona S., Garcia-Gonzalez P., Alarcon-Martin E., Valero S., Sotolongo-Grau O., Ullgren A., Naj A. C., Lemstra A. W., Benaque A., Perez-Cordon A., Benussi A., Rabano A., Padovani A., Squassina A., de Mendonca A., Arias Pastor A., Kok A. A. L., Meggy A., Pastor A. B., Espinosa A., Corma-Gomez A., Martin Montes A., Sanabria A., DeStefano A. L., Schneider A., Haapasalo A., Kinhult Stahlbom A., Tybjaerg-Hansen A., Hartmann A. M., Spottke A., Corbaton-Anchuelo A., Rongve A., Borroni B., Arosio B., Nacmias B., Nordestgaard B. G., Kunkle B. W., Charbonnier C., Abdelnour C., Masullo C., Martinez Rodriguez C., Munoz-Fernandez C., Dufouil C., Graff C., Ferreira C. B., Chillotti C., Reynolds C. A., Fenoglio C., Van Broeckhoven C., Clark C., Pisanu C., Satizabal C. L., Holmes C., Buiza-Rueda D., Aarsland D., Rujescu D., Alcolea D., Galimberti D., Wallon D., Seripa D., Grunblatt E., Dardiotis E., Duzel E., Scarpini E., Conti E., Rubino E., Gelpi E., Rodriguez-Rodriguez E., Duron E., Boerwinkle E., Ferri E., Tagliavini F., Kucukali F., Pasquier F., Sanchez-Garcia F., Mangialasche F., Jessen F., Nicolas G., Selbaek G., Ortega G., Chene G., Hadjigeorgiou G., Rossi G., Spalletta G., Giaccone G., Grande G., Binetti G., Papenberg G., Hampel H., Bailly H., Zetterberg H., Soininen H., Karlsson I. K., Alvarez I., Appollonio I., Giegling I., Skoog I., Saltvedt I., Rainero I., Rosas Allende I., Hort J., Diehl-Schmid J., Van Dongen J., Vidal J. -S., Lehtisalo J., Wiltfang J., Thomassen J. Q., Kornhuber J., Haines J. L., Vogelgsang J., Pineda J. A., Fortea J., Popp J., Deckert J., Buerger K., Morgan K., Fliessbach K., Sleegers K., Molina-Porcel L., Kilander L., Weinhold L., Farrer L. A., Wang L. -S., Kleineidam L., Farotti L., Parnetti L., Tremolizzo L., Hausner L., Benussi L., Froelich L., Ikram M. A., Deniz-Naranjo M. C., Tsolaki M., Rosende-Roca M., Lowenmark M., Hulsman M., Spallazzi M., Pericak-Vance M. A., Esiri M., Bernal Sanchez-Arjona M., Dalmasso M. C., Martinez-Larrad M. T., Arcaro M., Nothen M. M., Fernandez-Fuertes M., Dichgans M., Ingelsson M., Herrmann M. J., Scherer M., Vyhnalek M., Kosmidis M. H., Yannakoulia M., Schmid M., Ewers M., Heneka M. T., Wagner M., Scamosci M., Kivipelto M., Hiltunen M., Zulaica M., Alegret M., Fornage M., Roberto N., van Schoor N. M., Seidu N. M., Banaj N., Armstrong N. J., Scarmeas N., Scherbaum N., Goldhardt O., Hanon O., Peters O., Skrobot O. A., Quenez O., Lerch O., Bossu P., Caffarra P., Dionigi Rossi P., Sakka P., Mecocci P., Hoffmann P., Holmans P. A., Fischer P., Riederer P., Yang Q., Marshall R., Kalaria R. N., Mayeux R., Vandenberghe R., Cecchetti R., Ghidoni R., Frikke-Schmidt R., Sorbi S., Hagg S., Engelborghs S., Helisalmi S., Botne Sando S., Kern S., Archetti S., Boschi S., Fostinelli S., Gil S., Mendoza S., Mead S., Ciccone S., Djurovic S., Heilmann-Heimbach S., Riedel-Heller S., Kuulasmaa T., del Ser T., Lebouvier T., Polak T., Ngandu T., Grimmer T., Bessi V., Escott-Price V., Giedraitis V., Deramecourt V., Maier W., Jian X., Pijnenburg Y. A. L., Smith A. D., Saenz A., Bizzarro A., Lauria A., Vacca A., Solomon A., Anastasiou A., Richardson A., Boland A., Koivisto A., Daniele A., Greco A., Marianthi A., McGuinness B., Fin B., Ferrari C., Custodero C., Ferrarese C., Ingino C., Mangone C., Reyes Toso C., Martinez C., Cuesta C., Muchnik C., Joachim C., Ortiz C., Besse C., Johansson C., Zoia C. P., Laske C., Anastasiou C., Palacio D. L., Politis D. G., Janowitz D., Craig D., Mann D. M., Neary D., Jurgen D., Daian D., Belezhanska D., Kohler E., Castano E. M., Koutsouraki E., Chipi E., De Roeck E., Costantini E., Vardy E. R. L. C., Piras F., Roveta F., Prestia F. A., Assogna F., Salani F., Sala G., Lacidogna G., Novack G., Wilcock G., Thonberg H., Kolsch H., Weber H., Boecker H., Etchepareborda I., Piaceri I., Tuomilehto J., Lindstrom J., Laczo J., Johnston J., Deleuze J. -F., Harris J., Schott J. M., Priller J., Bacha J. I., Snowden J., Lisso J., Mihova K. Y., Traykov L., Morelli L., Brusco L. I., Rainer M., Takalo M., Bjerke M., Del Zompo M., Serpente M., Sanchez Abalos M., Rios M., Peltonen M., Herrman M. J., Kohler M., Rojo M., Jones M., Orsini M., Medel N., Olivar N., Fox N. C., Salvadori N., Hooper N. M., Galeano P., Solis P., Bastiani P., Passmore P., Heun R., Antikainen R., Olaso R., Perneczky R., Germani S., Lopez-Garcia S., Love S., Mehrabian S., Bagnoli S., Kochen S., Andreoni S., Teipel S., Todd S., Pickering-Brown S., Natunen T., Tegos T., Laatikainen T., Strandberg T., Polvikoski T. M., Matoska V., Ciullo V., Cores V., Solfrizzi V., Lisetti V., Sevillano Z., Aguilera N., Alarcon E., Boada M., Buendia M., Canabate P., Carracedo A., Diego S., Gailhajenet A., Guitart M., Ibarria M., Lafuente A., Maronas O., Martin E., Martinez M. T., Marquie M., Mauleon A., Moreno M., Orellana A., Pancho A., Peleja E., Preckler S., Real L. M., Ruiz A., Saez M. E., Serrano-Rios M., Tarraga L., Vargas L., Adarmes-Gomez A. D., Alonso M. D., Alvarez V., Amer-Ferrer G., Antequera M., Bernal M., Bullido M. J., Burguera J. A., Carrillo F., Carrion-Claro M., Casajeros M. J., Clarimon J., Cruz-Gamero J. M., de Pancorbo M. M., Escuela R., Garrote-Espina L., Garcia-Alberca J. M., Garcia Madrona S., Garcia-Ribas G., Gomez-Garre P., Hevilla S., Jesus S., Labrador Espinosa M. A., Legaz A., Lleo A., Lopez de Munain A., Macias-Garcia D., Manzanares S., Marin M., Marin-Munoz J., Marin T., Martinez B., Martinez V., Martinez-Lage Alvarez P., Medina M., Mendioroz Iriarte M., Mir P., Molinuevo J. L., Pastor P., Perez Tur J., Perinan-Tocino T., Pineda-Sanchez R., Pinol-Ripoll G., Real de Asua D., Rodrigo S., Sanchez del Valle Diaz R., Sanchez-Juan P., Sastre I., Vicente M. P., Vigo-Ortega R., Vivancos L., Macleod C., McCracken C., Brayne C., Bresner C., Grozeva D., Bellou E., Sommerville E. W., Matthews F., Leonenko G., Menzies G., Windle G., Harwood J., Phillips J., Bennett K., Luckuck L., Clare L., Woods R., Saad S., Burholt V., Kehoe P. G., Scheltens P., Holstege H., Amouyel P., Schellenberg G. D., Williams J., Seshadri S., van Duijn C. M., Mather K. A., Sanchez-Valle R., Blennow K., Huisman M., Andreassen O. A., Posthuma D., van der Flier W. M., Ramirez A., Lambert J. -C., and van der Lee S. J.

Abstract

The original version of this Article omitted from the author list the 212th author Patrizia Mecocci, who is from the Institute of Gerontology and Geriatrics, Department of Medicine, University of Perugia, Perugia, Italy. Consequently, the “Sample Contribution” section of Author Contributions was updated to add “P.M” between “P.D.” and “R.C.”. Additionally, the original version of this Article contained the incorrect affiliation for author Patrick Gavin Kehoe, which incorrectly read “German Center for Neurodegenerative Diseases (DZNE), Berlin, Germany”. The correct version replaces this affiliation with “Bristol Medical School (THS), University of Bristol, Southmead Hospital, Bristol, UK”. This has been corrected in both the PDF and HTML versions of the Article.

Published
2023

14. Cerebrospinal fluid markers including trefoil factor 3 are associated with neurodegeneration in amyloid-positive individuals.

Author

Paterson, RW, Bartlett, JW, Blennow, K, Fox, NC, Alzheimer's Disease Neuroimaging Initiative, Shaw, LM, Trojanowski, JQ, Zetterberg, H, and Schott, JM

Subjects
Alzheimer's Disease Neuroimaging Initiative, Brain, Cerebral Ventricles, Hippocampus, Humans, Alzheimer Disease, Amyloidosis, Atrophy, Peptides, tau Proteins, Mental Status Schedule, Aged, Aged, 80 and over, Female, Male, Apolipoprotein E4, Statistics as Topic, Cystatin C, Biomarkers, Trefoil Factor-3, Cognitive Dysfunction, and over, Psychology, Clinical Sciences, Public Health and Health Services
Abstract

We aimed to identify cerebrospinal fluid (CSF) biomarkers associated with neurodegeneration in individuals with and without CSF evidence of Alzheimer pathology. We investigated 287 Alzheimer's Disease Neuroimaging Initiative (ADNI) subjects (age=74.9±6.9; 22/48/30% with Alzheimer's disease/mild cognitive impairment/controls) with CSF multiplex analyte data and serial volumetric MRI. We calculated brain and hippocampal atrophy rates, ventricular expansion and Mini Mental State Examination decline. We used false discovery rate corrected regression analyses to assess associations between CSF variables and atrophy rates in individuals with and without amyloid pathology, adjusting in stages for tau, baseline volume, p-tau, age, sex, ApoE4 status and diagnosis. Analytes showing statistically significant independent relationships were entered into reverse stepwise analyses. Adjusting for tau, baseline volume, p-tau, age, sex and ApoE4, 4/83 analytes were significantly independently associated with brain atrophy rate, 1/83 with ventricular expansion and 2/83 with hippocampal atrophy. The strongest CSF predictor for the three atrophy measures was low trefoil factor 3 (TFF3). High cystatin C (CysC) was associated with higher whole brain atrophy and hippocampal atrophy rates. Lower levels of vascular endothelial growth factor and chromogranin A (CrA) were associated with higher whole brain atrophy. In exploratory reverse stepwise analyses, lower TFF3 was associated with higher rates of whole brain, hippocampal atrophy and ventricular expansion. Lower levels of CrA were associated with higher whole brain atrophy rate. The relationship between low TFF3 and increased hippocampal atrophy rate remained after adjustment for diagnosis. We identified a series of CSF markers that are independently associated with rate of neurodegeneration in amyloid-positive individuals. TFF3, a substrate for NOTCH processing may be an important biomarker of neurodegeneration across the Alzheimer spectrum.

Published
2014

15. Heart fatty acid binding protein and Aβ-associated Alzheimer's neurodegeneration

Author

Desikan, RS, Thompson, WK, Holland, D, Hess, CP, Brewer, JB, Zetterberg, H, Blennow, K, Andreassen, OA, McEvoy, LK, Hyman, BT, and Dale, AM

Abstract

Background: Epidemiological and molecular findings suggest a relationship between Alzheimer's disease (AD) and dyslipidemia, although the nature of this association is not well understood. Results: Using linear mixed effects models, we investigated the relationship between CSF levels of heart fatty acid binding protein (HFABP), a lipid binding protein involved with fatty acid metabolism and lipid transport, amyloid-β (Aβ), phospho-tau, and longitudinal MRI-based measures of brain atrophy among 295 non-demented and demented older individuals. Across all participants, we found a significant association of CSF HFABP with longitudinal atrophy of the entorhinal cortex and other AD-vulnerable neuroanatomic regions. However, we found that the relationship between CSF HABP and brain atrophy was significant only among those with low CSF Aβ1-42and occurred irrespective of phospho-tau181pstatus. Conclusions: Our findings indicate that Aβ-associated volume loss occurs in the presence of elevated HFABP irrespective of phospho-tau. This implicates a potentially important role for fatty acid binding proteins in Alzheimer's disease neurodegeneration. © 2013 Desikan et al.; licensee BioMed Central Ltd.

Published
2013

22. Effect of a 1-Year Nutritional Blend Supplementation on Plasma p-tau181 and GFAP Levels among Community-Dwelling Older Adults: A Secondary Analysis of the Nolan Trial

Author

Giudici, K.V., de Souto Barreto, P., Guyonnet, S., Cantet, C., Zetterberg, H., Boschat, C., Hudry, J., Andrieu, S., Schmitt, J.A.J., Vellas, B., and Blennow, K.

Subjects
Original Research
Abstract

BACKGROUND: Observational studies and some randomized controlled trials have suggested that nutritional supplementation could be a possible intervention pathway to prevent cognitive decline and Alzheimer’s disease (AD). As measuring amyloid-β and tau pathophysiology by positron emission tomography (PET) or cerebrospinal fluid (CSF) analyses may be perceived as complex, plasma versions of such biomarkers have emerged as more accessible alternatives with comparable capacity of predicting cognitive impairment. OBJECTIVES: This study aimed to evaluate the effect of a 1-year intervention with a nutritional blend on plasma p-tau181 and glial fibrillary acidic protein (GFAP) levels in community-dwelling older adults. Effects were further assessed in exploratory analyses within sub-cohorts stratified according to p-tau status (with the third tertile considered as high: ≥15.1 pg/ mL) and to apolipoprotein E (APOE) ε4 allele status. METHODS: A total of 289 participants ≥70 years (56.4% female, mean age 78.1 years, SD=4.7) of the randomized, double-blind, multicenter, placebo-controlled Nolan trial had their plasma p-tau181 assessed, and daily took either a nutritional blend (composed of thiamin, riboflavin, niacin, pantothenic acid, pyridoxine, biotin, folic acid, cobalamin, vitamin E, vitamin C, vitamin D, choline, selenium, citrulline, eicosapentaenoic acid – EPA, and docosahexaenoic acid – DHA) or placebo for 1 year. RESULTS: After 1-year, both groups presented a significant increase in plasma p-tau181 and GFAP values, with no effect of the intervention (p-tau181 between-group difference: 0.27pg/mL, 95%CI: -0.95, 1.48; p=0.665; GFAP between-group difference: -3.28 pg/mL, 95%CI: -17.25, 10.69; p=0.644). P-tau-and APOE ε4-stratified analyses provided similar findings. CONCLUSIONS: In community-dwelling older adults, we observed an increase in plasma p-tau181 and GFAP levels that was not different between the supplementation groups after one year.

Published
2023

23. Plasma neurofilament light chain level is not a biomarker of Charcot-Marie-Tooth disease progression: Results of 3-year follow-up study.

Author

Setlere, S., Grosmane, A., Kurjane, N., Gailite, L., Rots, D., Blennow, K., Zetterberg, H., Kenina, V., Setlere, S., Grosmane, A., Kurjane, N., Gailite, L., Rots, D., Blennow, K., Zetterberg, H., and Kenina, V.

Abstract

01 augustus 2023, Contains fulltext : 294542.pdf (Publisher’s version ) (Open Access), BACKGROUND AND PURPOSE: Charcot-Marie-Tooth disease (CMT) is a hereditary, slowly progressive neuropathy. Currently, there are no effective pharmacological treatments or sensitive disease activity biomarkers available. The aim of this study was to demonstrate the change in plasma neurofilament light chain (NfL) over time in a CMT cohort and analyse the association between CMT severity and NfL level. METHODS: Initially, 101 CMT patients and 64 controls were enrolled in the study. Repeated evaluation was performed in 73 patients and 28 controls at a 3-year interval. Disease severity assessment included clinical evaluation with CMT Neuropathy Score version 2 (CMTNSv2). Plasma NfL concentration was measured using the Simoa (single molecule array) NfL assay. RESULTS: Plasma NfL concentration was increased in the CMT group compared with controls (p < 0.001). Overall NfL level increased over the 3-year interval in both CMT (p = 0.012) and control (p = 0.001) groups. However, in 22 of 73 CMT patients and seven of 28 controls, the NfL level decreased from the baseline. Analysing the association between 3-year change in plasma NfL and disease severity (CMTNSv2), there was no correlation in the CMT group (r = 0.228, p = 0.052) or different CMT subgroups. CONCLUSIONS: Our study verifies increased plasma NfL concentrations in patients with CMT compared with controls. Longitudinal 3-year data showed a variable change in NfL levels between CMT subtypes. There was no association between change in NfL over time and disease severity. These findings suggests that NfL is not a biomarker for CMT progression.

Published
2023

25. Effect of a 1-Year Nutritional Blend Supplementation on Plasma p-tau181 and GFAP Levels among Community-Dwelling Older Adults: A Secondary Analysis of the Nolan Trial

Author

Giudici, K.V., primary, de Souto Barreto, P., additional, Guyonnet, S., additional, Cantet, C., additional, Zetterberg, H., additional, Boschat, C., additional, Hudry, J., additional, Andrieu, S., additional, Schmitt, J.A.J., additional, Vellas, B., additional, and Blennow, K., additional

Published
2023
Full Text
View/download PDF

27. Erratum to: Alzheimer’s Disease Composite Score: a Post-Hoc Analysis Using Data from the LipiDiDiet Trial in Prodromal Alzheimer’s Disease (The Journal of Prevention of Alzheimer's Disease, (2019), (1-5), 10.14283/jpad.2019.33)

Author

Hendrix, Suzanne B., Soininen, H., van Hees, A. M. J., Ellison, N., Visser, P. J., Solomon, A., Attali, A., Blennow, K., Kivipelto, M., Hartmann, T., Neurology, and Amsterdam Neuroscience - Neurodegeneration

Abstract

The article «Alzheimer’s Disease Composite Score: a Post-Hoc Analysis Using Data from the LipiDiDiet Trial in Prodromal Alzheimer’s Disease», written by S.B. Hendrix, H. Soininen, A.M.J. van Hees, N. Ellison, P.J. Visser, A. Solomon, A. Attali, K. Blennow, M. Kivipelto, T. Hartmann, was originally published electronically on the publisher’s internet portal (currently SpringerLink) on 10 September 2019 without open access.

Published
2023

28. Differential effects of familial Alzheimer’s disease-causing mutations on amyloid precursor protein (APP) trafficking, proteolytic conversion, and synaptogenic activity

Author

Schilling, S., Pradhan, A., Heesch, A., Helbig, A., Blennow, K., Koch, C., Bertgen, L., Koo, E., Brinkmalm, G., Zetterberg, H., Kins, S., and Eggert, S.

Abstract

Background: The amyloid precursor protein (APP), a synaptic adhesion molecule, is a key player in Alzheimer`s disease (AD) and the precursor of the Aβ peptide, which is generated by consecutive cleavages of β- and γ-secretases. Familial Alzheimer’s disease (FAD) describes a hereditary subgroup of AD that represents a low percentage of AD cases with an early onset of the disease. Different APP FAD mutations are thought to have qualitatively different effects on its proteolytic conversion. However, few studies have explored the pathogenic and putative physiological differences in more detail. Here, we compared different FAD mutations, located at the β- (Swedish), α- (Flemish, Arctic, Iowa) or γ-secretase (Iberian) cleavage sites. Methods: We examined heterologous expression of APP in WT and FAD mutants (Swedish, Flemish, Arctic, Iowa, Iberian) in non-neuronal cells and their impact on presynaptic differentiation in contacting axons of co-cultured neurons. To decipher the underlying molecular mechanism, we tested the subcellular localization, the endocytosis rate and the proteolytic processing in detail by immunoprecipitation–mass spectrometry. Results: Interestingly, we found that only the Iberian mutation showed altered synaptogenic function. Furthermore, the APP Iowa FAD mutant shows significantly decreased α-secretase processing which is in line with our results that APP carrying the Iowa mutation was significantly increased in early endosomes. However, most interestingly, immunoprecipitation–mass spectrometry analysis revealed that the amino acid substitutions of APP in FAD mutants have a decisive impact on their processing changes reflected in altered Aβ profiles. Importantly, N-terminally truncated Aβ peptides starting at position 5 were detected preferentially for APP Flemish, Arctic, and Iowa mutants containing amino acid substitutions around the α -secretase cleavage site. The strongest change in the ratio of Aβ40/Aβ42 was observed for the Iberian mutation while APP Swedish showed a substantial increase in Aβ1–17 peptides. Conclusions: Together, our data indicate that familial AD mutations located at the α-, β-, and γ-secretase cleavage sites show considerable differences in the underlying pathogenic mechanisms.

Published
2022

30. Neurotoxicity with high-dose disulfiram and vorinostat used for HIV latency reversal

Author

McMahon, J.H., Evans, V.A., Lau, J.S., Symons, J., Zerbato, J.M., Chang, J., Solomon, A., Tennakoon, S., Dantanarayana, A., Hagenauer, M., Lee, S., Palmer, S., Fisher, K., Bumpus, N., Heck, C.J.S., Burger, D.M., Wu, G., Zuck, P., Howell, B.J., Zetterberg, H.H., Blennow, K., Gisslen, M., Rasmussen, T.A., Lewin, S.R., McMahon, J.H., Evans, V.A., Lau, J.S., Symons, J., Zerbato, J.M., Chang, J., Solomon, A., Tennakoon, S., Dantanarayana, A., Hagenauer, M., Lee, S., Palmer, S., Fisher, K., Bumpus, N., Heck, C.J.S., Burger, D.M., Wu, G., Zuck, P., Howell, B.J., Zetterberg, H.H., Blennow, K., Gisslen, M., Rasmussen, T.A., and Lewin, S.R.

Abstract

Item does not contain fulltext, OBJECTIVE: The aim of this study was to examine whether administering both vorinostat and disulfiram to people with HIV (PWH) on antiretroviral therapy (ART) is well tolerated and can enhance HIV latency reversal. DESIGN: Vorinostat and disulfiram can increase HIV transcription in PWH on ART. Together, these agents may lead to significant HIV latency reversal. METHODS: Virologically suppressed PWH on ART received disulfiram 2000 mg daily for 28 days and vorinostat 400 mg daily on days 8-10 and 22-24. The primary endpoint was plasma HIV RNA on day 11 relative to baseline using a single copy assay. Assessments included cell-associated unspliced RNA as a marker of latency reversal, HIV DNA in CD4+ T-cells, plasma HIV RNA, and plasma concentrations of ART, vorinostat, and disulfiram. RESULTS: The first two participants (P1 and P2) experienced grade 3 neurotoxicity leading to trial suspension. After 24 days, P1 presented with confusion, lethargy, and ataxia having stopped disulfiram and ART. Symptoms resolved by day 29. After 11 days, P2 presented with paranoia, emotional lability, lethargy, ataxia, and study drugs were ceased. Symptoms resolved by day 23. CA-US RNA increased by 1.4-fold and 1.3-fold for P1 and P2 respectively. Plasma HIV RNA was detectable from day 8 to 37 (peak 81 copies ml-1) for P2 but was not increased in P1 Antiretroviral levels were therapeutic and neuronal injury markers were elevated in P1. CONCLUSION: The combination of prolonged high-dose disulfiram and vorinostat was not safe in PWH on ART and should not be pursued despite evidence of latency reversal.

Published
2022

31. Prevalence Estimates of Amyloid Abnormality Across the Alzheimer Disease Clinical Spectrum

Author

Jansen, W.J., Janssen, O., Tijms, B.M., Vos, S.J.B., Ossenkoppele, R., Visser, P.J., Group, A.B.S., Aarsland, D., Alcolea, D., Altomare, D., Arnim, C. von, Baiardi, S., Baldeiras, I., Barthel, H., Bateman, R.J., Berckel, B. Van, Binette, A.P., Blennow, K., Boada, M., Boecker, H., Bottlaender, M., Braber, A., Brooks, D.J., Buchem, M.A. van, Camus, V., Carill, J.M., Cerman, J., Chen, K., Chételat, G., Chipi, E., Cohen, A.D., Daniels, A., Delarue, M., Didic, M., Drzezga, A., Dubois, B., Eckerström, M., Ekblad, L.L., Engelborghs, S., Epelbaum, S., Fagan, A.M., Fan, Y., Fladby, T., Fleisher, A.S., Flier, W.M. van der, Förster, S., Fortea, J., Frederiksen, K.S., Freund-Levi, Y., Frings, L., Frisoni, G.B., Fröhlich, L., Gabryelewicz, T., Gertz, H.J., Gill, K.D., Gkatzima, O., Gómez-Tortosa, E., Grimmer, T., Guedj, E., Habeck, C.G., Hampel, H., Handels, R., Hansson, O., Hausner, L., Hellwig, S., Heneka, M.T., Herukka, S.K., Hildebrandt, H., Hodges, J., Hort, J., Huang, C.C., Iriondo, A.J., Itoh, Y., Ivanoiu, A., Jagust, W.J., Jessen, F., Johannsen, P., Johnson, K.A., Kandimalla, R., Kapaki, E.N., Kern, S., Kilander, L., Klimkowicz-Mrowiec, A., Klunk, W.E., Koglin, N., Kornhuber, J., Kramberger, M.G., Kuo, H.C., Laere, K. Van, Landau, S.M., Landeau, B., Lee, Dyantha I. van der, Leon, M., Leyton, C.E., Lin, K.J., Lleó, A., Löwenmark, M., Madsen, K., Maier, W., Marcusson, J., Olde Rikkert, M.G.M., Verbeek, M.M., Zboch, M., Zetterberg, H., Jansen, W.J., Janssen, O., Tijms, B.M., Vos, S.J.B., Ossenkoppele, R., Visser, P.J., Group, A.B.S., Aarsland, D., Alcolea, D., Altomare, D., Arnim, C. von, Baiardi, S., Baldeiras, I., Barthel, H., Bateman, R.J., Berckel, B. Van, Binette, A.P., Blennow, K., Boada, M., Boecker, H., Bottlaender, M., Braber, A., Brooks, D.J., Buchem, M.A. van, Camus, V., Carill, J.M., Cerman, J., Chen, K., Chételat, G., Chipi, E., Cohen, A.D., Daniels, A., Delarue, M., Didic, M., Drzezga, A., Dubois, B., Eckerström, M., Ekblad, L.L., Engelborghs, S., Epelbaum, S., Fagan, A.M., Fan, Y., Fladby, T., Fleisher, A.S., Flier, W.M. van der, Förster, S., Fortea, J., Frederiksen, K.S., Freund-Levi, Y., Frings, L., Frisoni, G.B., Fröhlich, L., Gabryelewicz, T., Gertz, H.J., Gill, K.D., Gkatzima, O., Gómez-Tortosa, E., Grimmer, T., Guedj, E., Habeck, C.G., Hampel, H., Handels, R., Hansson, O., Hausner, L., Hellwig, S., Heneka, M.T., Herukka, S.K., Hildebrandt, H., Hodges, J., Hort, J., Huang, C.C., Iriondo, A.J., Itoh, Y., Ivanoiu, A., Jagust, W.J., Jessen, F., Johannsen, P., Johnson, K.A., Kandimalla, R., Kapaki, E.N., Kern, S., Kilander, L., Klimkowicz-Mrowiec, A., Klunk, W.E., Koglin, N., Kornhuber, J., Kramberger, M.G., Kuo, H.C., Laere, K. Van, Landau, S.M., Landeau, B., Lee, Dyantha I. van der, Leon, M., Leyton, C.E., Lin, K.J., Lleó, A., Löwenmark, M., Madsen, K., Maier, W., Marcusson, J., Olde Rikkert, M.G.M., Verbeek, M.M., Zboch, M., and Zetterberg, H.

Abstract

Contains fulltext : 248802.pdf (Publisher’s version ) (Closed access)

Published
2022

32. Validation of the LUMIPULSE automated immunoassay for the measurement of core AD biomarkers in cerebrospinal fluid

Author

Gobom, J., Parnetti, L., Rosa-Neto, P., Vyhnalek, M., Gauthier, S., Cataldi, S., Lerch, O., Laczo, J., Cechova, K., Clarin, M., Benet, A.L., Pascoal, T.A., Rahmouni, N., Vandijck, M., Huyck, E., Bastard, N. Le, Stevenson, J., Chamoun, M., Alcolea, D., Lleó, A., Andreasson, U., Verbeek, M.M., Bellomo, G., Rinaldi, R., Ashton, N.J., Zetterberg, H., Sheardova, K., Hort, J., Blennow, K., Gobom, J., Parnetti, L., Rosa-Neto, P., Vyhnalek, M., Gauthier, S., Cataldi, S., Lerch, O., Laczo, J., Cechova, K., Clarin, M., Benet, A.L., Pascoal, T.A., Rahmouni, N., Vandijck, M., Huyck, E., Bastard, N. Le, Stevenson, J., Chamoun, M., Alcolea, D., Lleó, A., Andreasson, U., Verbeek, M.M., Bellomo, G., Rinaldi, R., Ashton, N.J., Zetterberg, H., Sheardova, K., Hort, J., and Blennow, K.

Abstract

Item does not contain fulltext

Published
2022

33. Cerebral biomarkers in neurologic complications of preeclampsia.

Author

Bergman, L, Hastie, R, Bokström-Rees, E, Zetterberg, H, Blennow, K, Schell, S, Imberg, H, Langenegger, E, Moodley, A, Walker, S, Tong, S, Cluver, C, Bergman, L, Hastie, R, Bokström-Rees, E, Zetterberg, H, Blennow, K, Schell, S, Imberg, H, Langenegger, E, Moodley, A, Walker, S, Tong, S, and Cluver, C

Abstract

BACKGROUND: There is no tool to accurately predict who is at risk of developing neurologic complications of preeclampsia, and there is no objective method to determine disease severity. OBJECTIVE: We assessed whether plasma concentrations of the cerebral biomarkers neurofilament light, tau, and glial fibrillary acidic protein could reflect disease severity in several phenotypes of preeclampsia. Furthermore, we compared the cerebral biomarkers with the angiogenic biomarkers soluble fms-like tyrosine kinase 1, placental growth factor, and soluble endoglin. STUDY DESIGN: In this observational study, we included women from the South African Preeclampsia Obstetric Adverse Events biobank. Plasma samples taken at diagnosis (preeclampsia cases) or admission for delivery (normotensive controls) were analyzed for concentrations of neurofilament light, tau, glial fibrillary acidic protein, placental growth factor, soluble fms-like tyrosine kinase 1, and soluble endoglin. The cerebrospinal fluid concentrations of inflammatory markers and albumin were analyzed in a subgroup of 15 women. Analyses were adjusted for gestational age, time from seizures and delivery to sampling, maternal age, and parity. RESULTS: Compared with 28 women with normotensive pregnancies, 146 women with preeclampsia demonstrated 2.18-fold higher plasma concentrations of neurofilament light (95% confidence interval, 1.64-2.88), 2.17-fold higher tau (95% confidence interval, 1.49-3.16), and 2.77-fold higher glial fibrillary acidic protein (95% confidence interval, 2.06-3.72). Overall, 72 women with neurologic complications (eclampsia, cortical blindness, and stroke) demonstrated increased plasma concentrations of tau (2.99-fold higher; 95% confidence interval, 1.92-4.65) and glial fibrillary acidic protein (3.22-fold higher; 95% confidence interval, 2.06-5.02) compared with women with preeclampsia without pulmonary edema; hemolysis, elevated liver enzymes, and low platelet count; or neurologic complications

Published
2022

34. Comparing the effect of xenon and sevoflurane anesthesia on postoperative neural injury biomarkers: a randomized controlled trial

Author

McGuigan, S, Evered, L, Scott, D, Silbert, B, Zetterberg, H, Blennow, K, McGuigan, S, Evered, L, Scott, D, Silbert, B, Zetterberg, H, and Blennow, K

Abstract

General anesthesia and surgery are associated with an increase in neural injury biomarkers. Elevations of these neural injury biomarkers in the perioperative period are associated with postoperative delirium. Xenon has been shown to be protective against a range of neurological insults in animal models. It remains to be seen if xenon anesthesia is neuroprotective in the perioperative setting in humans. Twenty-four participants scheduled for lithotripsy were randomized to receive either xenon or sevoflurane general anesthesia. There was no statistically significant difference in the concentrations of postoperative neural injury biomarkers between the xenon and sevoflurane group. Following the procedure there was a significant increase in the concentration from baseline of all three biomarkers at 1 hour post-induction with a return to baseline at 5 hours. General anesthesia for lithotripsy was associated with a significant increase at 1 hour post-induction in the neural injury biomarkers total tau, neurofilament light and tau phosphorylated at threonine 181, a marker of tau phosphorylation. The protocol was approved by the St. Vincent's Hospital Melbourne Ethics Committee (approval No. HREC/18/SVHM/221) on July 20, 2018 and was registered with the Australia New Zealand Clinical Trials Registry (registration No. ACTRN12618000916246) on May 31, 2018.

Published
2022

35. Cardiac troponin T is elevated and increases longitudinally in ALS patients

Author

Kläppe, U., Chamoun, S., Shen, Q., Finn, A., Evertsson, B., Zetterberg, H., Blennow, K., Press, R., Samuelsson, K., Månberg, Anna, Fang, F., Ingre, C., Kläppe, U., Chamoun, S., Shen, Q., Finn, A., Evertsson, B., Zetterberg, H., Blennow, K., Press, R., Samuelsson, K., Månberg, Anna, Fang, F., and Ingre, C.

Abstract

Objective: To test whether high-sensitivity cardiac troponin T (hs-cTnT) could act as a diagnostic or prognostic biomarker in ALS, comparing hs-cTnT to neurofilament light (NfL). Methods: We performed a case-control study, including 150 ALS patients, 28 ALS mimics, and 108 healthy controls, and a follow-up study of the ALS patients, during 2014–2020 in Stockholm, Sweden. We compared concentrations of hs-cTnT in plasma and NfL in the cerebrospinal fluid between cases and controls. To evaluate the diagnostic performance, we calculated the area under the curve (AUC). Hazard ratios (HRs) were estimated from Cox models to assess associations between hs-cTnT and NfL at ALS diagnosis and risk of death. The longitudinal analysis measured changes of hs-cTnT and NfL since ALS diagnosis. Results: We noted higher levels of hs-cTnT in ALS patients (median: 16.5 ng/L) than in ALS mimics (11 ng/L) and healthy controls (6 ng/L). Both hs-cTnT and NfL could distinguish ALS patients from ALS mimics, with higher AUC noted for NfL (AUC 0.88; 95%CI 0.79–0.97). Disease progression correlated weakly with hs-cTnT (Pearson’s r = 0.18, p = 0.04) and moderately with NfL (Pearson’s r = 0.41, p < 0.001). Shorter survival was associated with higher levels of NfL at diagnosis (HR 1.08, 95%CI 1.04–1.11), but not hs-cTnT. hs-cTnT increased (12.61 ng/L per year, 95%CI 7.14–18.06) whereas NfL decreased longitudinally since ALS diagnosis. Conclusions: NfL is a stronger diagnostic and prognostic biomarker than hs-cTnT for ALS. However, hs-cTnT might constitute a disease progression biomarker as it increases longitudinally. The underlying causes for this increase need to be investigated., QC 20220316

Published
2022
Full Text
View/download PDF

36. Clinical reporting following the quantification of cerebrospinal fluid biomarkers in Alzheimer's disease: An international overview

Author

Delaby, C., Teunissen, C.E., Blennow, K., Alcolea, D., Arisi, I., Amar, E.B., Beaume, A., Bedel, A., Bellomo, G., Bigot-Corbel, E., Bjerke, M., Blanc-Quintin, M.C., Boada, M., Bousiges, O., Chapman, M.D., DeMarco, M.L., D'Onofrio, M., Dumurgier, J., Dufour-Rainfray, D., Engelborghs, S., Esselmann, H., Fogli, A., Gabelle, A., Galloni, E., Gondolf, C., Grandhomme, F., Grau-Rivera, O., Hart, M., Ikeuchi, T., Jeromin, A., Kasuga, K., Keshavan, A., Khalil, M., Körtvelyessy, P., Kulczynska-Przybik, A., Laplanche, J.L., Lewczuk, P., Li, Q.X., Lleó, A., Malaplate, C., Marquié, M., Masters, C.L., Mroczko, B., Nogueira, L., Orellana, A., Otto, M., Oudart, J.B., Paquet, C., Paoletti, F.P., Parnetti, L., Perret-Liaudet, A., Peoc'h, K., Poesen, K., Puig-Pijoan, A., Quadrio, I., Quillard-Muraine, M., Rucheton, B., Schraen, S., Schott, J.M., Shaw, L.M., Suárez-Calvet, M., Tsolaki, M., Tumani, H., Udeh-Momoh, C.T., Vaudran, L., Verbeek, M.M., Verde, F., Vermunt, L., Vogelgsang, J., Wiltfang, J., Zetterberg, H., Lehmann, S., Delaby, C., Teunissen, C.E., Blennow, K., Alcolea, D., Arisi, I., Amar, E.B., Beaume, A., Bedel, A., Bellomo, G., Bigot-Corbel, E., Bjerke, M., Blanc-Quintin, M.C., Boada, M., Bousiges, O., Chapman, M.D., DeMarco, M.L., D'Onofrio, M., Dumurgier, J., Dufour-Rainfray, D., Engelborghs, S., Esselmann, H., Fogli, A., Gabelle, A., Galloni, E., Gondolf, C., Grandhomme, F., Grau-Rivera, O., Hart, M., Ikeuchi, T., Jeromin, A., Kasuga, K., Keshavan, A., Khalil, M., Körtvelyessy, P., Kulczynska-Przybik, A., Laplanche, J.L., Lewczuk, P., Li, Q.X., Lleó, A., Malaplate, C., Marquié, M., Masters, C.L., Mroczko, B., Nogueira, L., Orellana, A., Otto, M., Oudart, J.B., Paquet, C., Paoletti, F.P., Parnetti, L., Perret-Liaudet, A., Peoc'h, K., Poesen, K., Puig-Pijoan, A., Quadrio, I., Quillard-Muraine, M., Rucheton, B., Schraen, S., Schott, J.M., Shaw, L.M., Suárez-Calvet, M., Tsolaki, M., Tumani, H., Udeh-Momoh, C.T., Vaudran, L., Verbeek, M.M., Verde, F., Vermunt, L., Vogelgsang, J., Wiltfang, J., Zetterberg, H., and Lehmann, S.

Abstract

Item does not contain fulltext, INTRODUCTION: The current practice of quantifying cerebrospinal fluid (CSF) biomarkers as an aid in the diagnosis of Alzheimer's disease (AD) varies from center to center. For a same biochemical profile, interpretation and reporting of results may differ, which can lead to misunderstandings and raises questions about the commutability of tests. METHODS: We obtained a description of (pre-)analytical protocols and sample reports from 40 centers worldwide. A consensus approach allowed us to propose harmonized comments corresponding to the different CSF biomarker profiles observed in patients. RESULTS: The (pre-)analytical procedures were similar between centers. There was considerable heterogeneity in cutoff definitions and report comments. We therefore identified and selected by consensus the most accurate and informative comments regarding the interpretation of CSF biomarkers in the context of AD diagnosis. DISCUSSION: This is the first time that harmonized reports are proposed across worldwide specialized laboratories involved in the biochemical diagnosis of AD.

Published
2022

37. Chronic neuropsychiatric sequelae of SARS‐CoV‐2: Protocol and methods from the Alzheimer's Association Global Consortium

Author

de Erausquin, G.A., Snyder, H., Brugha, T.S., Seshadri, S., Carrillo, M., Sagar, R., Huang, Y., Newton, C., Tartaglia, C., Teunissen, C., Håkanson, K., Akinyemi, R., Prasad, K., D'Avossa, G., Gonzalez‐Aleman, G., Hosseini, A., Vavougios, G.D., Sachdev, P., Bankart, J., Mors, N.P.O., Lipton, R., Katz, M., Fox, P.T., Katshu, M.Z., Iyengar, M.S., Weinstein, G., Sohrabi, H.R., Jenkins, R., Stein, D.J., Hugon, J., Mavreas, V., Blangero, J., Cruchaga, C., Krishna, M., Wadoo, O., Becerra, R., Zwir, I., Longstreth, W.T., Kroenenberg, G., Edison, P., Mukaetova‐Ladinska, E., Staufenberg, E., Figueredo‐Aguiar, M., Yécora, A., Vaca, F., Zamponi, H.P., Re, V.L., Majid, A., Sundarakumar, J., Gonzalez, H.M., Geerlings, M.I., Skoog, I., Salmoiraghi, A., Boneschi, F.M., Patel, V.N., Santos, J.M., Arroyo, G.R., Moreno, A.C., Felix, P., Gallo, C., Arai, H., Yamada, M., Iwatsubo, T., Sharma, M., Chakraborty, N., Ferreccio, C., Akena, D., Brayne, C., Maestre, G., Blangero, S.W., Brusco, L.I., Siddarth, P., Hughes, T.M., Zuñiga, A.R., Kambeitz, J., Laza, A.R., Allen, N., Panos, S., Merrill, D., Ibáñez, A., Tsuang, D., Valishvili, N., Shrestha, S., Wang, S., Padma, V., Anstey, K.J., Ravindrdanath, V., Blennow, K., Mullins, P., Łojek, E., Pria, A., Mosley, T.H., Gowland, P., Girard, T.D., Bowtell, R., Vahidy, F.S., de Erausquin, G.A., Snyder, H., Brugha, T.S., Seshadri, S., Carrillo, M., Sagar, R., Huang, Y., Newton, C., Tartaglia, C., Teunissen, C., Håkanson, K., Akinyemi, R., Prasad, K., D'Avossa, G., Gonzalez‐Aleman, G., Hosseini, A., Vavougios, G.D., Sachdev, P., Bankart, J., Mors, N.P.O., Lipton, R., Katz, M., Fox, P.T., Katshu, M.Z., Iyengar, M.S., Weinstein, G., Sohrabi, H.R., Jenkins, R., Stein, D.J., Hugon, J., Mavreas, V., Blangero, J., Cruchaga, C., Krishna, M., Wadoo, O., Becerra, R., Zwir, I., Longstreth, W.T., Kroenenberg, G., Edison, P., Mukaetova‐Ladinska, E., Staufenberg, E., Figueredo‐Aguiar, M., Yécora, A., Vaca, F., Zamponi, H.P., Re, V.L., Majid, A., Sundarakumar, J., Gonzalez, H.M., Geerlings, M.I., Skoog, I., Salmoiraghi, A., Boneschi, F.M., Patel, V.N., Santos, J.M., Arroyo, G.R., Moreno, A.C., Felix, P., Gallo, C., Arai, H., Yamada, M., Iwatsubo, T., Sharma, M., Chakraborty, N., Ferreccio, C., Akena, D., Brayne, C., Maestre, G., Blangero, S.W., Brusco, L.I., Siddarth, P., Hughes, T.M., Zuñiga, A.R., Kambeitz, J., Laza, A.R., Allen, N., Panos, S., Merrill, D., Ibáñez, A., Tsuang, D., Valishvili, N., Shrestha, S., Wang, S., Padma, V., Anstey, K.J., Ravindrdanath, V., Blennow, K., Mullins, P., Łojek, E., Pria, A., Mosley, T.H., Gowland, P., Girard, T.D., Bowtell, R., and Vahidy, F.S.

Abstract

Introduction Coronavirus disease 2019 (COVID-19) has caused >3.5 million deaths worldwide and affected >160 million people. At least twice as many have been infected but remained asymptomatic or minimally symptomatic. COVID-19 includes central nervous system manifestations mediated by inflammation and cerebrovascular, anoxic, and/or viral neurotoxicity mechanisms. More than one third of patients with COVID-19 develop neurologic problems during the acute phase of the illness, including loss of sense of smell or taste, seizures, and stroke. Damage or functional changes to the brain may result in chronic sequelae. The risk of incident cognitive and neuropsychiatric complications appears independent from the severity of the original pulmonary illness. It behooves the scientific and medical community to attempt to understand the molecular and/or systemic factors linking COVID-19 to neurologic illness, both short and long term. Methods This article describes what is known so far in terms of links among COVID-19, the brain, neurological symptoms, and Alzheimer's disease (AD) and related dementias. We focus on risk factors and possible molecular, inflammatory, and viral mechanisms underlying neurological injury. We also provide a comprehensive description of the Alzheimer's Association Consortium on Chronic Neuropsychiatric Sequelae of SARS-CoV-2 infection (CNS SC2) harmonized methodology to address these questions using a worldwide network of researchers and institutions. Results Successful harmonization of designs and methods was achieved through a consensus process initially fragmented by specific interest groups (epidemiology, clinical assessments, cognitive evaluation, biomarkers, and neuroimaging). Conclusions from subcommittees were presented to the whole group and discussed extensively. Presently data collection is ongoing at 19 sites in 12 countries representing Asia, Africa, the Americas, and Europe. Discussion The Alzheimer's Association Global Consortium harmoni

Published
2022

38. Biomarkers of brain injury after cardiac arrest; a statistical analysis plan from the TTM2 trial biobank investigators.

Author

Moseby-Knappe, M, Levin, H, Blennow, K, Ullén, S, Zetterberg, H, Lilja, G, Dankiewicz, J, Jakobsen, JC, Lagebrant, A, Friberg, H, Nichol, A, Ainschough, K, Eastwood, GM, Wise, MP, Thomas, M, Keeble, T, Cariou, A, Leithner, C, Rylander, C, Düring, J, Bělohlávek, J, Grejs, A, Borgquist, O, Undén, J, Simon, M, Rolny, V, Piehler, A, Cronberg, T, Nielsen, N, Moseby-Knappe, M, Levin, H, Blennow, K, Ullén, S, Zetterberg, H, Lilja, G, Dankiewicz, J, Jakobsen, JC, Lagebrant, A, Friberg, H, Nichol, A, Ainschough, K, Eastwood, GM, Wise, MP, Thomas, M, Keeble, T, Cariou, A, Leithner, C, Rylander, C, Düring, J, Bělohlávek, J, Grejs, A, Borgquist, O, Undén, J, Simon, M, Rolny, V, Piehler, A, Cronberg, T, and Nielsen, N

Abstract

BACKGROUND: Several biochemical markers in blood correlate with the magnitude of brain injury and may be used to predict neurological outcome after cardiac arrest. We present a protocol for the evaluation of prognostic accuracy of brain injury markers after cardiac arrest. The aim is to define the best predictive marker and to establish clinically useful cut-off levels for routine implementation. METHODS: Prospective international multicenter trial within the Targeted Hypothermia versus Targeted Normothermia after Out-of-Hospital Cardiac Arrest (TTM2) trial in collaboration with Roche Diagnostics International AG. Samples were collected 0, 24, 48, and 72 hours after randomisation (serum) and 0 and 48 hours after randomisation (plasma), and pre-analytically processed at each site before storage in a central biobank. Routine markers neuron-specific enolase (NSE) and S100B, and neurofilament light, total-tau and glial fibrillary acidic protein will be batch analysed using novel Elecsys® electrochemiluminescence immunoassays on a Cobas e601 instrument. RESULTS: Statistical analysis will be reported according to the Standards for Reporting Diagnostic accuracy studies (STARD) and will include comparisons for prediction of good versus poor functional outcome at six months post-arrest, by modified Rankin Scale (0-3 vs. 4-6), using logistic regression models and receiver operating characteristics curves, evaluation of mortality at six months according to biomarker levels and establishment of cut-off values for prediction of poor neurological outcome at 95-100% specificities. CONCLUSIONS: This prospective trial may establish a standard methodology and clinically appropriate cut-off levels for the optimal biomarker of brain injury which predicts poor neurological outcome after cardiac arrest.

Published
2022

39. Cerebrospinal fluid neurofilament light chain differentiates primary psychiatric disorders from rapidly progressive, Alzheimer's disease and frontotemporal disorders in clinical settings

Author

Eratne, D, Loi, SM, Qiao-Xin, L, Stehmann, C, Malpas, CB, Santillo, A, Janelidze, S, Cadwallader, C, Walia, N, Ney, B, Lewis, V, Senesi, M, Fowler, C, McGlade, A, Varghese, S, Ravanfar, P, Kelso, W, Farrand, S, Keem, M, Kang, M, Goh, AMY, Dhiman, K, Gupta, V, Watson, R, Yassi, N, Kaylor-Hughes, C, Kanaan, R, Perucca, P, Dobson, H, Vivash, L, Ali, R, O'Brien, TJ, Hansson, O, Zetterberg, H, Blennow, K, Walterfang, M, Masters, CL, Berkovic, SF, Collins, S, Velakoulis, D, Eratne, D, Loi, SM, Qiao-Xin, L, Stehmann, C, Malpas, CB, Santillo, A, Janelidze, S, Cadwallader, C, Walia, N, Ney, B, Lewis, V, Senesi, M, Fowler, C, McGlade, A, Varghese, S, Ravanfar, P, Kelso, W, Farrand, S, Keem, M, Kang, M, Goh, AMY, Dhiman, K, Gupta, V, Watson, R, Yassi, N, Kaylor-Hughes, C, Kanaan, R, Perucca, P, Dobson, H, Vivash, L, Ali, R, O'Brien, TJ, Hansson, O, Zetterberg, H, Blennow, K, Walterfang, M, Masters, CL, Berkovic, SF, Collins, S, and Velakoulis, D

Abstract

INTRODUCTION: Many patients with cognitive and neuropsychiatric symptoms face diagnostic delay and misdiagnosis. We investigated whether cerebrospinal fluid (CSF) neurofilament light (NfL) and total-tau (t-tau) could assist in the clinical scenario of differentiating neurodegenerative (ND) from psychiatric disorders (PSY), and rapidly progressive disorders. METHODS: Biomarkers were examined in patients from specialist services (ND and PSY) and a national Creutzfeldt-Jakob registry (Creutzfeldt-Jakob disease [CJD] and rapidly progressive dementias/atypically rapid variants of common ND, RapidND). RESULTS: A total of 498 participants were included: 197 ND, 67 PSY, 161 CJD, 48 RapidND, and 20 controls. NfL was elevated in ND compared to PSY and controls, with highest levels in CJD and RapidND. NfL distinguished ND from PSY with 95%/78% positive/negative predictive value, 92%/87% sensitivity/specificity, 91% accuracy. NfL outperformed t-tau in most real-life clinical diagnostic dilemma scenarios, except distinguishing CJD from RapidND. DISCUSSION: We demonstrated strong generalizable evidence for the diagnostic utility of CSF NfL in differentiating ND from psychiatric disorders, with high accuracy.

Published
2022

40. Plasma neurofilament light chain protein is not increased in treatment-resistant schizophrenia and first-degree relatives

Author

Eratne, D, Janelidze, S, Malpas, CB, Loi, S, Walterfane, M, Merritt, A, Diouf, I, Blennow, K, Zetterberg, H, Cilia, B, Warman, C, Bousman, C, Everall, I, Zalesky, A, Jayaram, M, Thomas, N, Berkovic, SF, Hansson, O, Velakoulis, D, Pantelis, C, Santillo, A, Eratne, D, Janelidze, S, Malpas, CB, Loi, S, Walterfane, M, Merritt, A, Diouf, I, Blennow, K, Zetterberg, H, Cilia, B, Warman, C, Bousman, C, Everall, I, Zalesky, A, Jayaram, M, Thomas, N, Berkovic, SF, Hansson, O, Velakoulis, D, Pantelis, C, and Santillo, A

Abstract

OBJECTIVE: Schizophrenia, a complex psychiatric disorder, is often associated with cognitive, neurological and neuroimaging abnormalities. The processes underlying these abnormalities, and whether a subset of people with schizophrenia have a neuroprogressive or neurodegenerative component to schizophrenia, remain largely unknown. Examining fluid biomarkers of diverse types of neuronal damage could increase our understanding of these processes, as well as potentially provide clinically useful biomarkers, for example with assisting with differentiation from progressive neurodegenerative disorders such as Alzheimer and frontotemporal dementias. METHODS: This study measured plasma neurofilament light chain protein (NfL) using ultrasensitive Simoa technology, to investigate the degree of neuronal injury in a well-characterised cohort of people with treatment-resistant schizophrenia on clozapine (n = 82), compared to first-degree relatives (an at-risk group, n = 37), people with schizophrenia not treated with clozapine (n = 13), and age- and sex-matched controls (n = 59). RESULTS: We found no differences in NfL levels between treatment-resistant schizophrenia (mean NfL, M = 6.3 pg/mL, 95% confidence interval: [5.5, 7.2]), first-degree relatives (siblings, M = 6.7 pg/mL, 95% confidence interval: [5.2, 8.2]; parents, M after adjusting for age = 6.7 pg/mL, 95% confidence interval: [4.7, 8.8]), controls (M = 5.8 pg/mL, 95% confidence interval: [5.3, 6.3]) and not treated with clozapine (M = 4.9 pg/mL, 95% confidence interval: [4.0, 5.8]). Exploratory, hypothesis-generating analyses found weak correlations in treatment-resistant schizophrenia, between NfL and clozapine levels (Spearman's r = 0.258, 95% confidence interval: [0.034, 0.457]), dyslipidaemia (r = 0.280, 95% confidence interval: [0.064, 0.470]) and a negative correlation with weight (r = -0.305, 95% confidence interval: [-0.504, -0.076]). CONCLUSION: Treatment-resistant schizophrenia does not appear to be associated

Published
2022

41. Increase in Epstein Barr virus serologies precedes neuroaxonal damage in pre-symptomatic multiple sclerosis

Author

Jons, D., Bergström, T., Zetterberg, H., Biström, M., Alonso-Magdalena, L., Gunnarsson, Martin, Vrethem, M., Blennow, K., Nilsson, S., Huang, J., Kockum, I., Olsson, T., Waterboer, T., Sundström, P., Andersen, O., Jons, D., Bergström, T., Zetterberg, H., Biström, M., Alonso-Magdalena, L., Gunnarsson, Martin, Vrethem, M., Blennow, K., Nilsson, S., Huang, J., Kockum, I., Olsson, T., Waterboer, T., Sundström, P., and Andersen, O.

Abstract

Introduction: Epstein-Barr virus (EBV) infection may be a pre-condition for the development of multiple sclerosis (MS). EBV antibodies, predominantly anti-EBNA1, develop in the presymp-tomatic phase of virtually all MS patients. Using material from a serum repository, studies in advance of MS onset indicated that EBV seropositivity preceded the first expression of incipient axonal lesions, serum Neurofilament Light (sNFL) . Objectives: To determine the onset and individual order of appearance of EBV seroreactivity and the serum neuroaxonal injury marker neurofilament light (sNfL) in a wide age spectrum of presymptomatic MS patients. Aims: To characterize the presymptomatic appearance of anti-bodies against an intranuclear (EBNA1) and a surface EBV anti-gen (gp350) and sNfL.Methods: A nested case-control study in 669 pre-symptomati-cally acquired blood samples from persons who later received an MS diagnosis, and from 1:1 matched control persons. Serum lev-els of EBNA1, VCA and gp350 IgG antibodies and sNFL (n=519) were measured in individual presymptomatic samples and expressed as delta scores with matched controls in relation to time until MS onset. Results: Serum levels expressed as delta scores for anti EBV and NfL IgG showed an incipient increase for anti EBNA1 and gp350 from 15-20 years before MS debut. Significant (p=0.001 and p=0.002) from 10-15 years, with consistent delta-scores succes-sively closer to MS onset. These findings contrasted to the level of sNfL which increasingly diverged from matched controls from 5-10 years before the onset of MS. None of the individual sam-ples negative for both EBNA1 and VCA IgG antibodies in the pre-MS group (n = 36) showed any elevation of the sNfL level. Conclusions: In a pre-MS material, the seroreactivity against EBNA1 was followed by VCA and gp350, before increased sNFL appeared, indicating incipient axonal injury. Togeth

Published
2022

47. List of Contributors

Author

Avila, J., primary, Ballatore, C., additional, Bitan, G., additional, Blennow, K., additional, Brunden, K.R., additional, Cabezas-Opazo, F., additional, Carlson, M.C., additional, Castellani, R.J., additional, Chesser, A.S., additional, Correia, S.C., additional, Crehan, H., additional, Cummings, J.L., additional, Davies, P., additional, Gertsik, N., additional, Golde, T.E., additional, Haas, L.T., additional, Harrington, C.R., additional, Holtzman, D.M., additional, Hooli, B., additional, Hur, J.-Y., additional, Johnson, D.S., additional, Johnson, G.V.W., additional, Lee, V.M.-Y., additional, Lemere, C.A., additional, Lessard, C.B., additional, Li, H., additional, Li, Y.-M., additional, Liao, F., additional, Longo, F.M., additional, Massa, S.M., additional, Matthews, D.C., additional, Medina, M., additional, Moreira, P.I., additional, Nelson, A.R., additional, Pallo, S.P., additional, Perry, G., additional, Quintanilla, R.A., additional, Rahimi, F., additional, Ran, Y., additional, Sagare, A.P., additional, Schmidt, M.E., additional, Schneider, L.S., additional, Selkoe, D.J., additional, Simmons, D.A., additional, Sinha, S., additional, Smith, A.B., additional, Staelens, S., additional, Storey, J.M.D., additional, Strittmatter, S.M., additional, Tanzi, R.E., additional, Trojanowski, J.Q., additional, Vassar, R., additional, Wischik, C.M., additional, Wischik, D.J., additional, Wolfe, M.S., additional, Yang, T., additional, Zetterberg, H., additional, Zhong, K., additional, and Zlokavic, B.V., additional

Published
2016
Full Text
View/download PDF

49. Altered Balance of Reelin Proteolytic Fragments in the Cerebrospinal Fluid of Alzheimer's Disease Patients

Author

Lopez-Font I, Lennol M, Iborra-Lazaro G, Zetterberg H, Blennow K, and Saez-Valero J

Subjects
aggregate, reelin, biomarker, Alzheimer's disease, proteolytic fragment, cerebrospinal fluid
Abstract

Reelin binds to the apolipoprotein E receptor apoER2 to activate an intracellular signaling cascade. The proteolytic cleavage of reelin follows receptor binding but can also occur independently of its binding to receptors. This study assesses whether reelin proteolytic fragments are differentially affected in the cerebrospinal fluid (CSF) of Alzheimer's disease (AD) subjects. CSF reelin species were analyzed by Western blotting, employing antibodies against the N- and C-terminal domains. In AD patients, we found a decrease in the 420 kDa full-length reelin compared with controls. In these patients, we also found an increase in the N-terminal 310 kDa fragment resulting from the cleavage at the so-called C-t site, whereas the 180 kDa fragment originated from the N-t site remained unchanged. Regarding the C-terminal proteolytic fragments, the 100 kDa fragment resulting from the cleavage at the C-t site also displayed increased levels, whilst the one resulting from the N-t site, the 250 kDa fragment, decreased. We also detected the presence of an aberrant reelin species with a molecular mass of around 500 kDa present in AD samples (34 of 43 cases), while it was absent in the 14 control cases analyzed. These 500 kDa species were only immunoreactive to N-terminal antibodies. We validated the occurrence of these aberrant reelin species in an A beta 42-treated reelin-overexpressing cell model. When we compared the AD samples from APOE genotype subgroups, we only found minor differences in the levels of reelin fragments associated to the APOE genotype, but interestingly, the levels of fragments of apoER2 were lower in APOE epsilon 4 carriers with regards to APOE epsilon 3/epsilon 3. The altered proportion of reelin/apoER2 fragments and the occurrence of reelin aberrant species suggest a complex regulation of the reelin signaling pathway, which results impaired in AD subjects.

Published
2022

50. State-of-the-art of lumbar puncture and its place in the journey of patients with Alzheimer's disease

Author

Hampel, H, Shaw, LM, Aisen, P, Chen, C, Lleo, A, Iwatsubo, T, Iwata, A, Yamada, M, Ikeuchi, T, Jia, JP, Wang, HL, Teunissen, CE, Peskind, E, Blennow, K, Cummings, J, and Vergallo, A

Subjects
system readiness, diagnosis, biomarker, lumbar puncture, Alzheimer's disease, evidence-based guidelines, cerebrospinal fluid
Abstract

Recent advances in developing disease-modifying therapies (DMT) for Alzheimer's disease (AD), and the recognition that AD pathophysiology emerges decades before clinical symptoms, necessitate a paradigm shift of health-care systems toward biomarker-guided early detection, diagnosis, and therapeutic decision-making. Appropriate incorporation of cerebrospinal fluid biomarker analysis in clinical practice is an essential step toward system readiness for accommodating the demand of AD diagnosis and proper use of DMTs-once they become available. However, the use of lumbar puncture (LP) in individuals with suspected neurodegenerative diseases such as AD is inconsistent, and the perception of its utility and safety differs considerably among medical specialties as well as among regions and countries. This review describes the state-of-the-art evidence concerning the safety profile of LP in older adults, discusses the risk factors for LP-associated adverse events, and provides recommendations and an outlook for optimized use and global implementation of LP in individuals with suspected AD.

Published
2022

Catalog

Books, media, physical & digital resources
See catalog results