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822 results on '"St George Hyslop P"'

102. Investigation of C9orf72 in Four Neurodegenerative Disorders

Author

Rogaeva, E, Xi, Zr, Zinman, L, Grinberg, Y, Moreno, D, Sato, C, Bilbao, Jm, Ghani, M, Hernandez, I, Ruiz, A, Boada, M, Moron, Fj, Lang, Ae, Marras, C, Bruni, A, Colao, R, Maletta, Rg, Pinessi, Lorenzo, Rainero, Innocenzo, Galimberti, D, Morrison, K, Moorby, C, Stockton, Jd, Masellis, M, Black, Se, Hazrati, Ln, Fornazzari, L, Villagra, R, Rojas Garcia, R, Clarimon, J, Mayeux, R, Robertson, J, and St George Hyslop, P.

Subjects
Neurodegenerative Disorders, C9orf72
Published
2012

104. Molecular Genetic Strategies in Familial Alzheimer’s Disease: Theoretical and Practical Considerations

Author

St George-Hyslop, P. H., primary, Farrer, L., additional, Haines, J., additional, Myers, R., additional, Polinsky, R., additional, Nee, L., additional, Bruni, A., additional, Scorbi, S., additional, Piacentini, S., additional, Amaducci, L., additional, Foncin, J.-F., additional, Feldman, R. G., additional, Frommelt, P., additional, Watkins, P., additional, Tanzi, R., additional, Aalbo, J., additional, Growdon, J., additional, Drachman, D., additional, Pollen, D., additional, Conneally, P. M., additional, and Gusella, J., additional

Published
1988
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105. TMP21 is a presenilin complex component that modulates gamma- but not epsilon-secretase activities

Author

Chien, F., Hasegawa, H., Schmitt-Ulms, G., Kawarai, T., Bohm, C., Katayama, T., Gu, Yuqiao, Sanjo, N., Glista, M., Rogaeva, E., Wakutami, Y., Pardossi-Piquart, R., Ruan, X., Tandon, A., Checler, F., Marambaud, P., Hansen, K., Westaway, D., St. George-Hyslop, P., Fraser, P., Institut de pharmacologie moléculaire et cellulaire (IPMC), Université Nice Sophia Antipolis (... - 2019) (UNS), and COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-Centre National de la Recherche Scientifique (CNRS)

Subjects
[SDV.BBM]Life Sciences [q-bio]/Biochemistry, Molecular Biology
Published
2006

106. presenilin-dependent gamma-secretase-mediated control of p53-associated cell death in Alzheimer's disease

Author

Alves Da Costa, C., Sunyach, C., Pardossi-Piquart, R., Sevalle, J., Vincent, B., Boyer, N., Kawarai, T., Girardot, N., St. George-Hyslop, P., Checler, F., Institut de pharmacologie moléculaire et cellulaire (IPMC), Université Nice Sophia Antipolis (... - 2019) (UNS), and COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-Centre National de la Recherche Scientifique (CNRS)

Subjects
[SDV.BBM]Life Sciences [q-bio]/Biochemistry, Molecular Biology
Published
2006

107. Characterizing familial corticobasal syndrome due to Alzheimer's disease pathology and PSEN1 mutations.

Author

Lam, Benjamin, Khan, Aun, Keith, Julia, Rogaeva, Ekaterina, Bilbao, Juan, St. George-Hyslop, Peter, Ghani, Mahdi, Freedman, Morris, Stuss, Donald T., Chow, Tiffany, Black, Sandra E., and Masellis, Mario

Abstract

Introduction Corticobasal syndrome (CBS) resulting from genetic Alzheimer's disease (AD) has been described only once. Whether familial CBS-AD is a distinct clinical entity with its own imaging signature remains unknown. Methods Four individuals with CBS from two families underwent detailed assessment. For two individuals, regional atrophy and hypoperfusion were compared to autopsy-confirmed typical late-onset AD and corticobasal degeneration, as well as genetically proven PSEN1 cases with an amnestic presentation. Results One family harbored a novel mutation in PSEN1 :p.Phe283Leu. MRI demonstrated severe parietal, perirolandic, and temporal atrophy, with relative sparing of frontal and ipsilateral hippocampal regions. Autopsy confirmed pure AD pathology. The other family harbored a known PSEN1 mutation:p.Gly378Val. Discussion This report confirms familial CBS-AD as a distinct clinical entity, with a parietal-perirolandic-temporal atrophy signature. It illustrates the clinical heterogeneity that can occur despite a shared genetic cause and underscores the need for biomarkers such as amyloid imaging during life. [ABSTRACT FROM AUTHOR]

Published
2017
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108. JLK inhibitors: isocoumarin compounds as putative probes to selectively target the g-secretase pathway

Author

Checler, F., Alves Da Costa, C., Ayral, E., Andrau, D., Dumanchin-Njock, C., Farzan, M., Hernandez, J.F., Lefranc-Jullien, S., Marambaud, P., Pasini, A., Petit, A., Phiel, C., Robert, P., St George-Hyslop, P., Wilk, S., Institut de pharmacologie moléculaire et cellulaire (IPMC), Université Nice Sophia Antipolis (... - 2019) (UNS), and COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-Centre National de la Recherche Scientifique (CNRS)

Subjects
[SDV.BBM]Life Sciences [q-bio]/Biochemistry, Molecular Biology
Published
2005

109. Alzheimer's Abeta vaccination of rhesus monkeys (Macaca mulatta)

Author

Gandy, S, DeMattos, R B, Lemere, C A, Heppner, F L, Leverone, J, Aguzzi, A, Ershler, W B, Dai, J, Fraser, P, St George Hyslop, P, Holtzman, D M, Walker, L C, Keller, E T, University of Zurich, and Gandy, S

Subjects
1309 Developmental Biology, 1302 Aging, 10208 Institute of Neuropathology, 570 Life sciences, biology, 610 Medicine & health
Published
2004

110. Presenilin-directed inhibitors of ?-secretase trigger caspase 3 activation in presenilins-expressing and presenilins-deficient cells

Author

Alves Da Costa, C., Ayral, E., Hernandez, J.F., St. George-Hyslop, P., Checler, F., Institut de pharmacologie moléculaire et cellulaire (IPMC), Université Nice Sophia Antipolis (... - 2019) (UNS), and COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-Centre National de la Recherche Scientifique (CNRS)

Subjects
[SDV.BBM]Life Sciences [q-bio]/Biochemistry, Molecular Biology
Published
2004

111. Frontotemporal dementia and its subtypes: A genome-wide association study

Author

Ferrari, R, Hernandez, DG, Nalls, MA, Rohrer, JD, Ramasamy, A, Kwok, JBJ, Dobson-Stone, C, Brooks William S., BS, Schofield, PR, Halliday, GM, Hodges, JR, Piguet, O, Bartley, L, Thompson, E, Haan, E, Hernández, I, Ruiz, A, Boada, M, Borroni, B, Padovani, A, Cruchaga, C, Cairns, NJ, Benussi, L, Binetti, G, Ghidoni, R, Forloni, G, Galimberti, D, Fenoglio, C, Serpente, M, Scarpini, E, Clarimón, J, Lleó, A, Blesa, R, Waldö, ML, Nilsson, K, Nilsson, C, Mackenzie, IRA, Hsiung, GYR, Mann, DMA, Grafman, J, Morris, CM, Attems, J, Griffiths, TD, McKeith, IG, Thomas, AJ, Pietrini, P, Huey, ED, Wassermann, EM, Baborie, A, Jaros, E, Tierney, MC, Pastor, P, Razquin, C, Ortega-Cubero, S, Alonso, E, Perneczky, R, Diehl-Schmid, J, Alexopoulos, P, Kurz, A, Rainero, I, Rubino, E, Pinessi, L, Rogaeva, E, St George-Hyslop, P, Rossi, G, Tagliavini, F, Giaccone, G, Rowe, JB, Schlachetzki, JCM, Uphill, J, Collinge, J, Mead, S, Danek, A, Van Deerlin, VM, Grossman, M, Trojanowski, JQ, Van der Zee, J, Deschamps, W, Van Langenhove, T, Cruts, M, Van Broeckhoven, C, Cappa, SF, Le Ber, I, Hannequin, D, Golfier, V, Vercelletto, M, Brice, A, Nacmias, B, Sorbi, S, Bagnoli, S, Piaceri, I, Nielsen, JE, Hjermind, LE, Riemenschneider, M, Mayhaus, M, Ibach, B, Gasparoni, G, Pichler, S, Gu, W, Rossor, MN, Ferrari, R, Hernandez, DG, Nalls, MA, Rohrer, JD, Ramasamy, A, Kwok, JBJ, Dobson-Stone, C, Brooks William S., BS, Schofield, PR, Halliday, GM, Hodges, JR, Piguet, O, Bartley, L, Thompson, E, Haan, E, Hernández, I, Ruiz, A, Boada, M, Borroni, B, Padovani, A, Cruchaga, C, Cairns, NJ, Benussi, L, Binetti, G, Ghidoni, R, Forloni, G, Galimberti, D, Fenoglio, C, Serpente, M, Scarpini, E, Clarimón, J, Lleó, A, Blesa, R, Waldö, ML, Nilsson, K, Nilsson, C, Mackenzie, IRA, Hsiung, GYR, Mann, DMA, Grafman, J, Morris, CM, Attems, J, Griffiths, TD, McKeith, IG, Thomas, AJ, Pietrini, P, Huey, ED, Wassermann, EM, Baborie, A, Jaros, E, Tierney, MC, Pastor, P, Razquin, C, Ortega-Cubero, S, Alonso, E, Perneczky, R, Diehl-Schmid, J, Alexopoulos, P, Kurz, A, Rainero, I, Rubino, E, Pinessi, L, Rogaeva, E, St George-Hyslop, P, Rossi, G, Tagliavini, F, Giaccone, G, Rowe, JB, Schlachetzki, JCM, Uphill, J, Collinge, J, Mead, S, Danek, A, Van Deerlin, VM, Grossman, M, Trojanowski, JQ, Van der Zee, J, Deschamps, W, Van Langenhove, T, Cruts, M, Van Broeckhoven, C, Cappa, SF, Le Ber, I, Hannequin, D, Golfier, V, Vercelletto, M, Brice, A, Nacmias, B, Sorbi, S, Bagnoli, S, Piaceri, I, Nielsen, JE, Hjermind, LE, Riemenschneider, M, Mayhaus, M, Ibach, B, Gasparoni, G, Pichler, S, Gu, W, and Rossor, MN

Abstract

Background: Frontotemporal dementia (FTD) is a complex disorder characterised by a broad range of clinical manifestations, differential pathological signatures, and genetic variability. Mutations in three genes-MAPT, GRN, and C9orf72-have been associated with FTD. We sought to identify novel genetic risk loci associated with the disorder. Methods: We did a two-stage genome-wide association study on clinical FTD, analysing samples from 3526 patients with FTD and 9402 healthy controls. To reduce genetic heterogeneity, all participants were of European ancestry. In the discovery phase (samples from 2154 patients with FTD and 4308 controls), we did separate association analyses for each FTD subtype (behavioural variant FTD, semantic dementia, progressive non-fluent aphasia, and FTD overlapping with motor neuron disease [FTD-MND]), followed by a meta-analysis of the entire dataset. We carried forward replication of the novel suggestive loci in an independent sample series (samples from 1372 patients and 5094 controls) and then did joint phase and brain expression and methylation quantitative trait loci analyses for the associated (p<5 × 10-8) single-nucleotide polymorphisms. Findings: We identified novel associations exceeding the genome-wide significance threshold (p<5 × 10-8). Combined (joint) analyses of discovery and replication phases showed genome-wide significant association at 6p21.3, HLA locus (immune system), for rs9268877 (p=1·05 × 10-8; odds ratio=1·204 [95% CI 1·11-1·30]), rs9268856 (p=5·51 × 10-9; 0·809 [0·76-0·86]) and rs1980493 (p value=1·57 × 10-8, 0·775 [0·69-0·86]) in the entire cohort. We also identified a potential novel locus at 11q14, encompassing RAB38/CTSC (the transcripts of which are related to lysosomal biology), for the behavioural FTD subtype for which joint analyses showed suggestive association for rs302668 (p=2·44 × 10-7; 0·814 [0·71-0·92]). Analysis of expression and methylation quantitative trait loci data suggested that these loci migh

Published
2014

112. Gene-wide analysis detects two new susceptibility genes for Alzheimer's disease

Author

Escott-Price, V, Bellenguez, C, Wang, LS, Choi, SH, Harold, D, Jones, L, Holmans, P, Gerrish, A, Vedernikov, A, Richards, A, DeStefano, AL, Lambert, JC, Ibrahim-Verbaas, CA, Naj, AC, Sims, R, Jun, G, Bis, JC, Beecham, GW, Grenier-Boley, B, Russo, G, Thornton-Wells, TA, Denning, N, Smith, AV, Chouraki, V, Thomas, C, Arfan Ikram, M, Zelenika, D, Vardarajan, BN, Kamatani, Y, Lin, CF, Schmidt, H, Kunkle, B, Dunstan, ML, Vronskaya, M, Johnson, AD, Ruiz, A, Bihoreau, MT, Reitz, C, Pasquier, F, Hollingworth, P, Hanon, O, Fitzpatrick, AL, Buxbaum, JD, Campion, D, Crane, PK, Becker, CBT, Gudnason, V, Cruchaga, C, Craig, D, Amin, N, Berr, C, Lopez, OL, De Jager, PL, Deramecourt, V, Johnston, JA, Evans, D, Lovestone, S, Letenneur, L, Hernández, I, Rubinsztein, DC, Eiriksdottir, G, Sleegers, K, Goate, AM, Fiévet, N, Huentelman, MJ, Gill, M, Brown, K, Kamboh, MI, Keller, L, Barberger-Gateau, P, McGuinness, B, Larson, EB, Myers, AJ, Dufouil, C, Todd, S, Wallon, D, Love, S, Rogaeva, E, Gallacher, J, St George-Hyslop, P, Clarimon, J, Lleo, A, Bayer, A, Tsuang, DW, Yu, L, Tsolaki, M, Bossù, P, Spalletta, G, Proitsi, P, Collinge, J, Sorbi, S, Sanchez Garcia, F, Fox, NC, Hardy, J, Naranjo, MCD, Bosco, P, Clarke, R, Brayne, C, Galimberti, D, Scarpini, E, Escott-Price, V, Bellenguez, C, Wang, LS, Choi, SH, Harold, D, Jones, L, Holmans, P, Gerrish, A, Vedernikov, A, Richards, A, DeStefano, AL, Lambert, JC, Ibrahim-Verbaas, CA, Naj, AC, Sims, R, Jun, G, Bis, JC, Beecham, GW, Grenier-Boley, B, Russo, G, Thornton-Wells, TA, Denning, N, Smith, AV, Chouraki, V, Thomas, C, Arfan Ikram, M, Zelenika, D, Vardarajan, BN, Kamatani, Y, Lin, CF, Schmidt, H, Kunkle, B, Dunstan, ML, Vronskaya, M, Johnson, AD, Ruiz, A, Bihoreau, MT, Reitz, C, Pasquier, F, Hollingworth, P, Hanon, O, Fitzpatrick, AL, Buxbaum, JD, Campion, D, Crane, PK, Becker, CBT, Gudnason, V, Cruchaga, C, Craig, D, Amin, N, Berr, C, Lopez, OL, De Jager, PL, Deramecourt, V, Johnston, JA, Evans, D, Lovestone, S, Letenneur, L, Hernández, I, Rubinsztein, DC, Eiriksdottir, G, Sleegers, K, Goate, AM, Fiévet, N, Huentelman, MJ, Gill, M, Brown, K, Kamboh, MI, Keller, L, Barberger-Gateau, P, McGuinness, B, Larson, EB, Myers, AJ, Dufouil, C, Todd, S, Wallon, D, Love, S, Rogaeva, E, Gallacher, J, St George-Hyslop, P, Clarimon, J, Lleo, A, Bayer, A, Tsuang, DW, Yu, L, Tsolaki, M, Bossù, P, Spalletta, G, Proitsi, P, Collinge, J, Sorbi, S, Sanchez Garcia, F, Fox, NC, Hardy, J, Naranjo, MCD, Bosco, P, Clarke, R, Brayne, C, Galimberti, D, and Scarpini, E

Abstract

Background: Alzheimer's disease is a common debilitating dementia with known heritability, for which 20 late onset susceptibility loci have been identified, but more remain to be discovered. This study sought to identify new susceptibility genes, using an alternative gene-wide analytical approach which tests for patterns of association within genes, in the powerful genome-wide association dataset of the International Genomics of Alzheimer's Project Consortium, comprising over 7 m genotypes from 25,580 Alzheimer's cases and 48,466 controls. Principal Findings: In addition to earlier reported genes, we detected genome-wide significant loci on chromosomes 8 (TP53INP1, p = 1.4×10-6) and 14 (IGHV1-67 p = 7.9×10-8) which indexed novel susceptibility loci. Significance: The additional genes identified in this study, have an array of functions previously implicated in Alzheimer's disease, including aspects of energy metabolism, protein degradation and the immune system and add further weight to these pathways as potential therapeutic targets in Alzheimer's disease.

Published
2014

113. Latrepirdine improves cognition and arrests progression of neuropathology in an Alzheimer's mouse model

Author

Steele, J, Lachenmayer, M, Ju, S, Stock, A, Liken, J, Kim, S, Delgado, L, Alfaro, I, Bernales, S, Verdile, G, Bharadwaj, P, Gupta, V, Barr, R, Friss, A, Dolios, G, Wang, R, Ringe, D, Fraser, P, Westaway, D, St George-Hyslop, P, Szabo, P, Relkin, N, Buxbaum, J, Glabe, C, Protter, A, Martins, R, Ehrlich, M, Petsko, G, Yue, Z, Gandy, S, Steele, J, Lachenmayer, M, Ju, S, Stock, A, Liken, J, Kim, S, Delgado, L, Alfaro, I, Bernales, S, Verdile, G, Bharadwaj, P, Gupta, V, Barr, R, Friss, A, Dolios, G, Wang, R, Ringe, D, Fraser, P, Westaway, D, St George-Hyslop, P, Szabo, P, Relkin, N, Buxbaum, J, Glabe, C, Protter, A, Martins, R, Ehrlich, M, Petsko, G, Yue, Z, and Gandy, S

Abstract

Latrepirdine (Dimebon) is a pro-neurogenic, antihistaminic compound that has yielded mixed results in clinical trials of mild to moderate Alzheimer's disease, with a dramatically positive outcome in a Russian clinical trial that was unconfirmed in a replication trial in the United States. We sought to determine whether latrepirdine (LAT)-stimulated amyloid precursor protein (APP) catabolism is at least partially attributable to regulation of macroautophagy, a highly conserved protein catabolism pathway that is known to be impaired in brains of patients with Alzheimer's disease (AD). We utilized several mammalian cellular models to determine whether LAT regulates mammalian target of rapamycin (mTOR) and Atg5-dependent autophagy. Male TgCRND8 mice were chronically administered LAT prior to behavior analysis in the cued and contextual fear conditioning paradigm, as well as immunohistological and biochemical analysis of AD-related neuropathology. Treatment of cultured mammalian cells with LAT led to enhanced mTOR- and Atg5-dependent autophagy. Latrepirdine treatment of TgCRND8 transgenic mice was associated with improved learning behavior and with a reduction in accumulation of Aβ42 and α-synuclein. We conclude that LAT possesses pro-autophagic properties in addition to the previously reported pro-neurogenic properties, both of which are potentially relevant to the treatment and/or prevention of neurodegenerative diseases. We suggest that elucidation of the molecular mechanism(s) underlying LAT effects on neurogenesis, autophagy and behavior might warranty the further study of LAT as a potentially viable lead compound that might yield more consistent clinical benefit following the optimization of its pro-neurogenic, pro-autophagic and/or pro-cognitive activities. © 2013 Macmillan Publishers Limited.

Published
2013

114. Identification of common variants influencing risk of the tauopathy progressive supranuclear palsy

Author

Hoglinger, G. (Gunter), Melhem, N.M. (Nadine), Dickson, D. (Dennis), Sleiman, P.M.A. (Patrick), Wang, L.S. (Li-San), Klei, L. (Lambertus), Rademakers, R. (Rosa), Silva, R. (Rohan) de, Litvan, I. (Irene), Riley, D.E. (David), Swieten, J.C. (John) van, Heutink, P. (Peter), Wszolek, Z.K. (Zbigniew), Uitti, R.J. (Ryan), Vandrovcova, J. (Jana), Hurtig, H.I. (Howard), Gross, R.G. (Rachel), Maetzler, W. (Walter), Goldwurm, S. (Stefano), Tolosa, E., Borroni, B. (Barbara), Pastor, P. (Pau), Cantwell, L.B. (Laura), Han, M.R., Dillman, A. (Allissa), Brug, M.P. (Marcel) van der, Gibbs, J. (Raphael), Cookson, M.R. (Mark), Hernandez, D.G. (Dena), Singleton, A. (Andrew), Farrer, M.J. (Matthew), Yu, C.-E. (Changen), Golbe, L.I. (Lawrence), Revesz, T. (Tamas), Hardy, J. (John), Lees, A.J. (Andrew), Devlin, B. (Bernie), Hakonarson, H. (Hakon), Müller, U. (Ulrich), Schellenberg, G.D. (Gerard), Albin, R.L. (Roger), Alonso, E. (Elena), Apfelbacher, M. (Manuela), Arnold, S.E. (Steven), Avila, J. (Jesús), Beach, T.G. (Thomas), Beecher, S. (Sherry), Berg, D. (Daniela), Bird, T.D. (Thomas), Bogdanović, N. (Nenad), Boon, A.J.W. (Andrea), Bordelon, Y. (Yvette), Brice, A. (Alexis), Budka, H. (Herbert), Canesi, M. (Margherita), Chiu, W.Z. (Wang Zheng), Cilia, R. (Roberto), Colosimo, C. (Carlo), Deyn, P.P. (Peter) de, Yebenes, J.G. de, Donker Kaat, L. (Laura), Duara, R. (Ranjan), Durr, A., Engelborghs, S. (Sebastiaan), Fabbrini, G. (Giovanni), Finch, N.A. (Nicole), Flook, R. (Robyn), Frosch, M.P. (Matthew), Gaig, C., Galasko, D. (Douglas), Gasser, T. (Thomas), Gearing, M. (Marla), Geller, E.T. (Evan), Ghetti, B. (Bernardino), Graff-Radford, N.R. (Neill), Grossman, M. (Murray), Hall, D.A. (Deborah), Hazrati, L.-N., Höllerhage, M. (Matthias), Jankovic, J. (Joseph), Juncos, J.L. (Jorge), Karydas, A. (Anna), Kretzschmar, H.A. (Hans), Leber, I. (Isabelle), Lee, V.M.Y. (Virginia), Lieberman, A.P. (Andrew), Lyons, K.E. (Kelly), Mariani, C. (Claudio), Masliah, E. (Eliezer), Massey, L.A. (Luke), McLean, C.A. (Catriona), Meucci, N. (Nicoletta), Miller, B.L. (Bruce), Mollenhauer, B. (Brit), Möller, J.C. (Jens), Morris, H. (Huw), O'Sullivan, S.S. (Sean), Oertel, W., Ottaviani, D. (Donatella), Padovani, A. (Alessandro), Pahwa, R. (Rajesh), Pezzoli, G. (Gianni), Pickering-Brown, S. (Stuart), Poewe, W. (Werner), Rabano, A. (Alberto), Rajput, A. (Alex), Reich, S.G. (Stephen), Respondek, G. (Gesine), Roeber, S. (Sigrun), Rohrer, J.D. (Jonathan), Ross, O.A. (Owen), Rossor, M. (Martin), Sacilotto, G. (Giorgio), Seeley, W.W. (William), Seppi, K. (Klaus), Silveira-Moriyama, L. (Laura), Spina, S. (Salvatore), Srulijes, K. (Karin), St. George-Hyslop, P. (Peter), Stamelou, M. (Maria), Standaert, D.G. (David), Tesei, S. (Silvana), Tourtellotte, W.W. (Wallace), Trenkwalder, C. (Claudia), Troakes, C. (Claire), Trojanowski, J.Q. (John), Troncoso, J.C. (Juan), Deerlin, V.M. (Vivianna), Vonsattel, J.P.G., Wenning, G.K. (Gregor), White III, C.L. (Charles), Winter, P. (Pia), Zarow, C. (Chris), Zecchinelli, A.L. (Anna), Antonini, A. (Angelo), Hoglinger, G. (Gunter), Melhem, N.M. (Nadine), Dickson, D. (Dennis), Sleiman, P.M.A. (Patrick), Wang, L.S. (Li-San), Klei, L. (Lambertus), Rademakers, R. (Rosa), Silva, R. (Rohan) de, Litvan, I. (Irene), Riley, D.E. (David), Swieten, J.C. (John) van, Heutink, P. (Peter), Wszolek, Z.K. (Zbigniew), Uitti, R.J. (Ryan), Vandrovcova, J. (Jana), Hurtig, H.I. (Howard), Gross, R.G. (Rachel), Maetzler, W. (Walter), Goldwurm, S. (Stefano), Tolosa, E., Borroni, B. (Barbara), Pastor, P. (Pau), Cantwell, L.B. (Laura), Han, M.R., Dillman, A. (Allissa), Brug, M.P. (Marcel) van der, Gibbs, J. (Raphael), Cookson, M.R. (Mark), Hernandez, D.G. (Dena), Singleton, A. (Andrew), Farrer, M.J. (Matthew), Yu, C.-E. (Changen), Golbe, L.I. (Lawrence), Revesz, T. (Tamas), Hardy, J. (John), Lees, A.J. (Andrew), Devlin, B. (Bernie), Hakonarson, H. (Hakon), Müller, U. (Ulrich), Schellenberg, G.D. (Gerard), Albin, R.L. (Roger), Alonso, E. (Elena), Apfelbacher, M. (Manuela), Arnold, S.E. (Steven), Avila, J. (Jesús), Beach, T.G. (Thomas), Beecher, S. (Sherry), Berg, D. (Daniela), Bird, T.D. (Thomas), Bogdanović, N. (Nenad), Boon, A.J.W. (Andrea), Bordelon, Y. (Yvette), Brice, A. (Alexis), Budka, H. (Herbert), Canesi, M. (Margherita), Chiu, W.Z. (Wang Zheng), Cilia, R. (Roberto), Colosimo, C. (Carlo), Deyn, P.P. (Peter) de, Yebenes, J.G. de, Donker Kaat, L. (Laura), Duara, R. (Ranjan), Durr, A., Engelborghs, S. (Sebastiaan), Fabbrini, G. (Giovanni), Finch, N.A. (Nicole), Flook, R. (Robyn), Frosch, M.P. (Matthew), Gaig, C., Galasko, D. (Douglas), Gasser, T. (Thomas), Gearing, M. (Marla), Geller, E.T. (Evan), Ghetti, B. (Bernardino), Graff-Radford, N.R. (Neill), Grossman, M. (Murray), Hall, D.A. (Deborah), Hazrati, L.-N., Höllerhage, M. (Matthias), Jankovic, J. (Joseph), Juncos, J.L. (Jorge), Karydas, A. (Anna), Kretzschmar, H.A. (Hans), Leber, I. (Isabelle), Lee, V.M.Y. (Virginia), Lieberman, A.P. (Andrew), Lyons, K.E. (Kelly), Mariani, C. (Claudio), Masliah, E. (Eliezer), Massey, L.A. (Luke), McLean, C.A. (Catriona), Meucci, N. (Nicoletta), Miller, B.L. (Bruce), Mollenhauer, B. (Brit), Möller, J.C. (Jens), Morris, H. (Huw), O'Sullivan, S.S. (Sean), Oertel, W., Ottaviani, D. (Donatella), Padovani, A. (Alessandro), Pahwa, R. (Rajesh), Pezzoli, G. (Gianni), Pickering-Brown, S. (Stuart), Poewe, W. (Werner), Rabano, A. (Alberto), Rajput, A. (Alex), Reich, S.G. (Stephen), Respondek, G. (Gesine), Roeber, S. (Sigrun), Rohrer, J.D. (Jonathan), Ross, O.A. (Owen), Rossor, M. (Martin), Sacilotto, G. (Giorgio), Seeley, W.W. (William), Seppi, K. (Klaus), Silveira-Moriyama, L. (Laura), Spina, S. (Salvatore), Srulijes, K. (Karin), St. George-Hyslop, P. (Peter), Stamelou, M. (Maria), Standaert, D.G. (David), Tesei, S. (Silvana), Tourtellotte, W.W. (Wallace), Trenkwalder, C. (Claudia), Troakes, C. (Claire), Trojanowski, J.Q. (John), Troncoso, J.C. (Juan), Deerlin, V.M. (Vivianna), Vonsattel, J.P.G., Wenning, G.K. (Gregor), White III, C.L. (Charles), Winter, P. (Pia), Zarow, C. (Chris), Zecchinelli, A.L. (Anna), and Antonini, A. (Angelo)

Abstract

Progressive supranuclear palsy (PSP) is a movement disorder with prominent tau neuropathology. Brain diseases with abnormal tau deposits are called tauopath

Published
2011
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117. Latrepirdine improves cognition and arrests progression of neuropathology in an Alzheimer's mouse model

Author

Steele, J W, primary, Lachenmayer, M L, additional, Ju, S, additional, Stock, A, additional, Liken, J, additional, Kim, S H, additional, Delgado, L M, additional, Alfaro, I E, additional, Bernales, S, additional, Verdile, G, additional, Bharadwaj, P, additional, Gupta, V, additional, Barr, R, additional, Friss, A, additional, Dolios, G, additional, Wang, R, additional, Ringe, D, additional, Fraser, P, additional, Westaway, D, additional, St George-Hyslop, P H, additional, Szabo, P, additional, Relkin, N R, additional, Buxbaum, J D, additional, Glabe, C G, additional, Protter, A A, additional, Martins, R N, additional, Ehrlich, M E, additional, Petsko, G A, additional, Yue, Z, additional, and Gandy, S, additional

Published
2012
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119. No evidence for tau duplications in frontal temporal dementia families showing genetic linkage to the tau locus in which tau mutations have not been found.

Author

Johnson, J, Ostojic, J, Lannfelt, L, Glaser, A, Basun, H, Rogaeva, E, Kawarai, T, Bruni, A, St George Hyslop, P H, Goate, A, Pastor, P, Chakraverty, S, Norton, J, Morris, J C, Hardy, J, Singleton, A, Johnson, J, Ostojic, J, Lannfelt, L, Glaser, A, Basun, H, Rogaeva, E, Kawarai, T, Bruni, A, St George Hyslop, P H, Goate, A, Pastor, P, Chakraverty, S, Norton, J, Morris, J C, Hardy, J, and Singleton, A

Published
2004

121. Medical missions for the provision of paediatric cardiac surgery in low- and middle-income countries

Author

Molloy, Frank J., Nguyen, Nguyenvu, Mize, Marisa, Wright, Gavin, St. George-Hyslop, Cecilia, O’Callaghan, Maura, Scanlan, Emma, and Novick, William M.

Abstract

AbstractThis review will outline the role of visiting cardiac surgical teams in low- and middle-income countries drawing on the collective experience of the authors in a wide range of locations. Requests for assistance can emerge from local programmes at a beginner or advanced stage. However, in all circumstances, careful pre-trip planning is necessary in conjunction with clinical and non-clinical local partners. The clinical evaluation, surgical procedures, and postoperative care all serve as a template for collaboration and education between the visiting and local teams in every aspect of care. Education focusses on both common and patient-specific issues. Case selection must appropriately balance the clinical priorities, safety, and educational objectives within the time constraints of trip duration. Considerable communication and practical challenges will present, and clinicians may need to make significant adjustments to their usual practice in order to function effectively in a resource-limited, unfamiliar, and multilingual environment. The effectiveness of visiting trips should be measured and constantly evaluated. Local and visiting teams should use data-driven evaluations of measurable outcomes and critical qualitative evaluation to repeatedly re-assess their interim goals. Progress invariably takes several years to achieve the final goal: an autonomous self-governing, self-financed, cardiac programme capable of providing care for children with complex CHD. This outcome is consistent with redundancy for the visiting trips model at the site, although fraternal, professional, and academic links will invariably remain for many years.

Published
2017
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122. Rare coding variants in PLCG2, ABI3, and TREM2 implicate microglial-mediated innate immunity in Alzheimer's disease

Author

Sims, Rebecca, van der Lee, Sven J, Naj, Adam C, Bellenguez, Céline, Badarinarayan, Nandini, Jakobsdottir, Johanna, Kunkle, Brian W, Boland, Anne, Raybould, Rachel, Bis, Joshua C, Martin, Eden R, Grenier-Boley, Benjamin, Heilmann-Heimbach, Stefanie, Chouraki, Vincent, Kuzma, Amanda B, Sleegers, Kristel, Vronskaya, Maria, Ruiz, Agustin, Graham, Robert R, Olaso, Robert, Hoffmann, Per, Grove, Megan L, Vardarajan, Badri N, Hiltunen, Mikko, Nöthen, Markus M, White, Charles C, Hamilton-Nelson, Kara L, Epelbaum, Jacques, Maier, Wolfgang, Choi, Seung-Hoan, Beecham, Gary W, Dulary, Cécile, Herms, Stefan, Smith, Albert V, Funk, Cory C, Derbois, Céline, Forstner, Andreas J, Ahmad, Shahzad, Li, Hongdong, Bacq, Delphine, Harold, Denise, Satizabal, Claudia L, Valladares, Otto, Squassina, Alessio, Thomas, Rhodri, Brody, Jennifer A, Qu, Liming, Sánchez-Juan, Pascual, Morgan, Taniesha, Wolters, Frank J, Zhao, Yi, Garcia, Florentino Sanchez, Denning, Nicola, Fornage, Myriam, Malamon, John, Naranjo, Maria Candida Deniz, Majounie, Elisa, Mosley, Thomas H, Dombroski, Beth, Wallon, David, Lupton, Michelle K, Dupuis, Josée, Whitehead, Patrice, Fratiglioni, Laura, Medway, Christopher, Jian, Xueqiu, Mukherjee, Shubhabrata, Keller, Lina, Brown, Kristelle, Lin, Honghuang, Cantwell, Laura B, Panza, Francesco, McGuinness, Bernadette, Moreno-Grau, Sonia, Burgess, Jeremy D, Solfrizzi, Vincenzo, Proitsi, Petra, Adams, Hieab H, Allen, Mariet, Seripa, Davide, Pastor, Pau, Cupples, L Adrienne, Price, Nathan D, Hannequin, Didier, Frank-García, Ana, Levy, Daniel, Chakrabarty, Paramita, Caffarra, Paolo, Giegling, Ina, Beiser, Alexa S, Giedraitis, Vilmantas, Hampel, Harald, Garcia, Melissa E, Wang, Xue, Lannfelt, Lars, Mecocci, Patrizia, Eiriksdottir, Gudny, Crane, Paul K, Pasquier, Florence, Boccardi, Virginia, Henández, Isabel, Barber, Robert C, Scherer, Martin, Tarraga, Lluis, Adams, Perrie M, Leber, Markus, Chen, Yuning, Albert, Marilyn S, Riedel-Heller, Steffi, Emilsson, Valur, Beekly, Duane, Braae, Anne, Schmidt, Reinhold, Blacker, Deborah, Masullo, Carlo, Schmidt, Helena, Doody, Rachelle S, Spalletta, Gianfranco, Jr, W T Longstreth, Fairchild, Thomas J, Bossù, Paola, Lopez, Oscar L, Frosch, Matthew P, Sacchinelli, Eleonora, Ghetti, Bernardino, Yang, Qiong, Huebinger, Ryan M, Jessen, Frank, Li, Shuo, Kamboh, M Ilyas, Morris, John, Sotolongo-Grau, Oscar, Katz, Mindy J, Corcoran, Chris, Dunstan, Melanie, Braddel, Amy, Thomas, Charlene, Meggy, Alun, Marshall, Rachel, Gerrish, Amy, Chapman, Jade, Aguilar, Miquel, Taylor, Sarah, Hill, Matt, Fairén, Mònica Díez, Hodges, Angela, Vellas, Bruno, Soininen, Hilkka, Kloszewska, Iwona, Daniilidou, Makrina, Uphill, James, Patel, Yogen, Hughes, Joseph T, Lord, Jenny, Turton, James, Hartmann, Annette M, Cecchetti, Roberta, Fenoglio, Chiara, Serpente, Maria, Arcaro, Marina, Caltagirone, Carlo, Orfei, Maria Donata, Ciaramella, Antonio, Pichler, Sabrina, Mayhaus, Manuel, Gu, Wei, Lleó, Alberto, Fortea, Juan, Blesa, Rafael, Barber, Imelda S, Brookes, Keeley, Cupidi, Chiara, Maletta, Raffaele Giovanni, Carrell, David, Sorbi, Sandro, Moebus, Susanne, Urbano, Maria, Pilotto, Alberto, Kornhuber, Johannes, Bosco, Paolo, Todd, Stephen, Craig, David, Johnston, Janet, Gill, Michael, Lawlor, Brian, Lynch, Aoibhinn, Fox, Nick C, Hardy, John, Albin, Roger L, Apostolova, Liana G, Arnold, Steven E, Asthana, Sanjay, Atwood, Craig S, Baldwin, Clinton T, Barnes, Lisa L, Barral, Sandra, Beach, Thomas G, Becker, James T, Bigio, Eileen H, Bird, Thomas D, Boeve, Bradley F, Bowen, James D, Boxer, Adam, Burke, James R, Burns, Jeffrey M, Buxbaum, Joseph D, Cairns, Nigel J, Cao, Chuanhai, Carlson, Chris S, Carlsson, Cynthia M, Carney, Regina M, Carrasquillo, Minerva M, Carroll, Steven L, Diaz, Carolina Ceballos, Chui, Helena C, Clark, David G, Cribbs, David H, Crocco, Elizabeth A, DeCarli, Charles, Dick, Malcolm, Duara, Ranjan, Evans, Denis A, Faber, Kelley M, Fallon, Kenneth B, Fardo, David W, Farlow, Martin R, Ferris, Steven, Foroud, Tatiana M, Galasko, Douglas R, Gearing, Marla, Geschwind, Daniel H, Gilbert, John R, Graff-Radford, Neill R, Green, Robert C, Growdon, John H, Hamilton, Ronald L, Harrell, Lindy E, Honig, Lawrence S, Huentelman, Matthew J, Hulette, Christine M, Hyman, Bradley T, Jarvik, Gail P, Abner, Erin, Jin, Lee-Way, Jun, Gyungah, Karydas, Anna, Kaye, Jeffrey A, Kim, Ronald, Kowall, Neil W, Kramer, Joel H, LaFerla, Frank M, Lah, James J, Leverenz, James B, Levey, Allan I, Li, Ge, Lieberman, Andrew P, Lunetta, Kathryn L, Lyketsos, Constantine G, Marson, Daniel C, Martiniuk, Frank, Mash, Deborah C, Masliah, Eliezer, McCormick, Wayne C, McCurry, Susan M, McDavid, Andrew N, McKee, Ann C, Mesulam, Marsel, Miller, Bruce L, Miller, Carol A, Miller, Joshua W, Morris, John C, Murrell, Jill R, Myers, Amanda J, O'Bryant, Sid, Olichney, John M, Pankratz, Vernon S, Parisi, Joseph E, Paulson, Henry L, Perry, William, Peskind, Elaine, Pierce, Aimee, Poon, Wayne W, Potter, Huntington, Quinn, Joseph F, Raj, Ashok, Raskind, Murray, Reisberg, Barry, Reitz, Christiane, Ringman, John M, Roberson, Erik D, Rogaeva, Ekaterina, Rosen, Howard J, Rosenberg, Roger N, Sager, Mark A, Saykin, Andrew J, Schneider, Julie A, Schneider, Lon S, Seeley, William W, Smith, Amanda G, Sonnen, Joshua A, Spina, Salvatore, Stern, Robert A, Swerdlow, Russell H, Tanzi, Rudolph E, Thornton-Wells, Tricia A, Trojanowski, John Q, Troncoso, Juan C, Van Deerlin, Vivianna M, Van Eldik, Linda J, Vinters, Harry V, Vonsattel, Jean Paul, Weintraub, Sandra, Welsh-Bohmer, Kathleen A, Wilhelmsen, Kirk C, Williamson, Jennifer, Wingo, Thomas S, Woltjer, Randall L, Wright, Clinton B, Yu, Chang-En, Yu, Lei, Garzia, Fabienne, Golamaully, Feroze, Septier, Gislain, Engelborghs, Sebastien, Vandenberghe, Rik, De Deyn, Peter P, Fernadez, Carmen Muñoz, Benito, Yoland Aladro, Thonberg, Hakan, Forsell, Charlotte, Lilius, Lena, Kinhult-Stählbom, Anne, Kilander, Lena, Brundin, RoseMarie, Concari, Letizia, Helisalmi, Seppo, Koivisto, Anne Maria, Haapasalo, Annakaisa, Dermecourt, Vincent, Fievet, Nathalie, Hanon, Olivier, Dufouil, Carole, Brice, Alexis, Ritchie, Karen, Dubois, Bruno, Himali, Jayanadra J, Keene, C Dirk, Tschanz, JoAnn, Fitzpatrick, Annette L, Kukull, Walter A, Norton, Maria, Aspelund, Thor, Larson, Eric B, Munger, Ron, Rotter, Jerome I, Lipton, Richard B, Bullido, María J, Hofman, Albert, Montine, Thomas J, Coto, Eliecer, Boerwinkle, Eric, Petersen, Ronald C, Alvarez, Victoria, Rivadeneira, Fernando, Reiman, Eric M, Gallo, Maura, O'Donnell, Christopher J, Reisch, Joan S, Bruni, Amalia Cecilia, Royall, Donald R, Dichgans, Martin, Sano, Mary, Galimberti, Daniela, St George-Hyslop, Peter, Scarpini, Elio, Tsuang, Debby W, Mancuso, Michelangelo, Bonuccelli, Ubaldo, Winslow, Ashley R, Daniele, Antonio, Wu, Chuang-Kuo, Peters, Oliver, Nacmias, Benedetta, Riemenschneider, Matthias, Heun, Reinhard, Brayne, Carol, Rubinsztein, David C, Bras, Jose, Guerreiro, Rita, Al-Chalabi, Ammar, Shaw, Christopher E, Collinge, John, Mann, David, Tsolaki, Magda, Clarimón, Jordi, Sussams, Rebecca, Lovestone, Simon, O'Donovan, Michael C, Owen, Michael J, Behrens, Timothy W, Mead, Simon, Goate, Alison M, Uitterlinden, Andre G, Holmes, Clive, Cruchaga, Carlos, Ingelsson, Martin, Bennett, David A, Powell, John, Golde, Todd E, Graff, Caroline, De Jager, Philip L, Morgan, Kevin, Ertekin-Taner, Nilufer, Combarros, Onofre, Psaty, Bruce M, Passmore, Peter, Younkin, Steven G, Berr, Claudine, Gudnason, Vilmundur, Rujescu, Dan, Dickson, Dennis W, Dartigues, Jean-François, DeStefano, Anita L, Ortega-Cubero, Sara, Hakonarson, Hakon, Campion, Dominique, Boada, Merce, Kauwe, John Keoni, Farrer, Lindsay A, Van Broeckhoven, Christine, Ikram, M Arfan, Jones, Lesley, Haines, Jonathan L, Tzourio, Christophe, Launer, Lenore J, Escott-Price, Valentina, Mayeux, Richard, Deleuze, Jean-François, Amin, Najaf, Holmans, Peter A, Pericak-Vance, Margaret A, Amouyel, Philippe, van Duijn, Cornelia M, Ramirez, Alfredo, Wang, Li-San, Lambert, Jean-Charles, Seshadri, Sudha, Williams, Julie, and Schellenberg, Gerard D

Abstract

We identified rare coding variants associated with Alzheimer's disease in a three-stage case–control study of 85,133 subjects. In stage 1, we genotyped 34,174 samples using a whole-exome microarray. In stage 2, we tested associated variants (P < 1 × 10−4) in 35,962 independent samples using de novo genotyping and imputed genotypes. In stage 3, we used an additional 14,997 samples to test the most significant stage 2 associations (P < 5 × 10−8) using imputed genotypes. We observed three new genome-wide significant nonsynonymous variants associated with Alzheimer's disease: a protective variant in PLCG2 (rs72824905: p.Pro522Arg, P = 5.38 × 10−10, odds ratio (OR) = 0.68, minor allele frequency (MAF)cases= 0.0059, MAFcontrols= 0.0093), a risk variant in ABI3 (rs616338: p.Ser209Phe, P = 4.56 × 10−10, OR = 1.43, MAFcases= 0.011, MAFcontrols= 0.008), and a new genome-wide significant variant in TREM2 (rs143332484: p.Arg62His, P = 1.55 × 10−14, OR = 1.67, MAFcases= 0.0143, MAFcontrols= 0.0089), a known susceptibility gene for Alzheimer's disease. These protein-altering changes are in genes highly expressed in microglia and highlight an immune-related protein–protein interaction network enriched for previously identified risk genes in Alzheimer's disease. These genetic findings provide additional evidence that the microglia-mediated innate immune response contributes directly to the development of Alzheimer's disease.

Published
2017
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124. Association of apolipoprotein E allele 4 with late-onset familial and sporadic Alzheimer's disease

Author

Saunders, A. M., primary, Strittmatter, W. J., additional, Schmechel, D., additional, St. George-Hyslop, P. H., additional, Pericak-Vance, M. A., additional, Joo, S. H., additional, Rosi, B. L., additional, Gusella, J. F., additional, Crapper-MacLachlan, D. R., additional, Alberts, M. J., additional, Hulette, C., additional, Crain, B., additional, Goldgaber, D., additional, and Roses, A. D., additional

Published
2011
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126. Worldwide distribution of PSEN1 Met146Leu mutation: A large variability for a founder mutation

Author

Bruni, A. C., primary, Bernardi, L., additional, Colao, R., additional, Rubino, E., additional, Smirne, N., additional, Frangipane, F., additional, Terni, B., additional, Curcio, S.A.M., additional, Mirabelli, M., additional, Clodomiro, A., additional, Di Lorenzo, R., additional, Maletta, R., additional, Anfossi, M., additional, Gallo, M., additional, Geracitano, S., additional, Tomaino, C., additional, Muraca, M. G., additional, Leotta, A., additional, Lio, S. G., additional, Pinessi, L., additional, Rainero, I., additional, Sorbi, S., additional, Nee, L., additional, Milan, G., additional, Pappata, S., additional, Postiglione, A., additional, Abbamondi, N., additional, Forloni, G., additional, St. George Hyslop, P., additional, Rogaeva, E., additional, Bugiani, O., additional, Giaccone, G., additional, Foncin, J. F., additional, Spillantini, M. G., additional, and Puccio, G., additional

Published
2010
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129. Alzheimer's Disease and Possible Gene Interaction

Author

St George-Hyslop, P., McLachlan, D. Crapper, Tuda, T., Rogaev, E., Karlinsky, H., Lippa, C. F., Pollen, D., Pericak-Vance, M. A., Corder, E. H., Saunders, A. M., Gaskill, P. C., Strittmatter, W. J., Roses, A. D., Schmechel, D. E., Small, G. W., and Haines, J. L.

Published
1994

130. Loss of -Secretase Function Impairs Endocytosis of Lipoprotein Particles and Membrane Cholesterol Homeostasis

Author

Tamboli, I. Y., primary, Prager, K., additional, Thal, D. R., additional, Thelen, K. M., additional, Dewachter, I., additional, Pietrzik, C. U., additional, St. George-Hyslop, P., additional, Sisodia, S. S., additional, De Strooper, B., additional, Heneka, M. T., additional, Filippov, M. A., additional, Muller, U., additional, van Leuven, F., additional, Lutjohann, D., additional, and Walter, J., additional

Published
2008
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131. Assessment of amyloid b-protein precursor gene mutations in a large set of familiar and sporadic Alzheimer's disease cases

Author

Tanzi, R. E., Vaula, G., Romano, D. M., Mortilla, M., Huang, T. L., Tupler, Rossella, Wasco, W., Hyman, B. T., Haines, J. L., Jenkins, B. J., Kalaitsidaki, M., Warren, A. C., Mcinnis, M. C., Antonarakis, S. E., Karlinsky, H., Percy, M. E., Connor, L., Growdon, J., Crapper McIachlan, D. R., Gusella, J. F., and St George Hyslop, P. H.

Subjects
Male, Recombination, Genetic, Base Sequence, beta Amyloid Protein Precursor gene, polymorphism, familial Alzheimer's disease, DNA Mutational Analysis, Molecular Sequence Data, Valine, DNA, Original Articles, Middle Aged, Polymerase Chain Reaction, Pedigree, Amyloid beta-Protein Precursor, Alzheimer Disease, mental disorders, Mutation, Humans, heterocyclic compounds, Isoleucine
Abstract

A genetic locus associated with familial Alzheimer disease (FAD) and a candidate gene, APP, encoding the amyloid protein precursor have both been assigned previously to chromosome 21, and, in a few FAD families, mutations of APP have been detected. However, obligate crossovers between APP and FAD have also been reported in several FAD pedigrees, including FAD4, a large kindred showing highly suggestive evidence for linkage of the disorder to chromosome 21. In case the apparent APP crossover in FAD4 actually represented an intragenic recombination event or segregation of different mutations in different family branches, we have performed a more detailed assessment of APP as a candidate gene in this family. The entire coding region of the APP gene was sequenced for FAD4 and for FAD1, a second large kindred. No mutations were found, indicating that, in at least one chromosome 21-linked FAD pedigree, the gene defect is not accounted for by a mutation in the known coding region of the APP gene. A total of 25 well-characterized early- and late-onset FAD pedigrees were typed for genetic linkage to APP, to assess the percentage of FAD families predicted to carry mutations in the APP gene. None of the FAD families yielded positive lod scores at a recombination fraction of 0.0. To estimate the overall prevalence of FAD-associated mutations in the beta A4 domain of APP, we sequenced exons 16 and 17 in 30 (20 early- and 10 late-onset) FAD kindreds and in 11 sporadic AD cases, and we screened 56 FAD kindreds and 81 cases of sporadic AD for the presence of the originally reported FAD-associated mutation, APP717 Val----Ile (by BclI digestion). No APP gene mutations were found in any of the FAD families or sporadic-AD samples examined in this study, suggesting that the mutations in exons 16 and 17 are a rare cause of FAD. Overall, these data suggest that APP gene mutations account for a very small portion of FAD.

Published
1992

132. Heterogeneity within a large kindred with frontotemporal dementia

Author

Bruni, A. C., primary, Momeni, P., additional, Bernardi, L., additional, Tomaino, C., additional, Frangipane, F., additional, Elder, J., additional, Kawarai, T., additional, Sato, C., additional, Pradella, S., additional, Wakutani, Y., additional, Anfossi, M., additional, Gallo, M., additional, Geracitano, S., additional, Costanzo, A., additional, Smirne, N., additional, Curcio, S.A.M., additional, Mirabelli, M., additional, Puccio, G., additional, Colao, R., additional, Maletta, R. G., additional, Kertesz, A., additional, St. George-Hyslop, P., additional, Hardy, J., additional, and Rogaeva, E., additional

Published
2007
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133. Massachusetts Alzheimer's Disease Research Center: Progress and challenges.

Author

Hyman, Bradley T., Growdon, John H., Albers, Mark W., Buckner, Randy L., Chhatwal, Jasmeer, Gomez-Isla, Maria Teresa, Haass, Christian, Hudry, Eloise, Jr.Jack, Clifford R., Johnson, Keith A., Khachaturian, Zaven S., Kim, Doo Yeon, Martin, Joseph B., Nitsch, Roger M., Rosen, Bruce R., Selkoe, Dennis J., Sperling, Reisa A., St George-Hyslop, Peter, Tanzi, Rudolph E., and Yap, Liang

Published
2015
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138. Genetic linkage studies suggest that Alzheimer's disease is not a single homogeneous disorder

Author

St George Hyslop, P. H., Haines, J. L., Farrer, L. A., Polinsky, R., Van Broeckhoven, C., Goate, A., Crapper McLachlan, D. R., Orr, H., Bruni, A. C., Sorbi††, S., Rainero, I., Foncin, J. F., Pollen, D., Cantu, J. M., Tupler, Rossella, Voskresenskaya, N., Mayeux, R., Growdon, J., Fried, V. A., Myers, R. H., Nee, L., Backhovens, H., Martin, J. J., Rossor, M., Owen, M. J., Mullan, M., Percy, M. E., Karlinsky, H., Rich, S., Heston, L., Montesi, M., Mortilla, M., Nacmias, N., Gusella, J. F., and Hardy, J. A.

Subjects
linkage analysis, familial Alzheimer's disease, genetic heterogeneity
Published
1990

140. P4-076 Polymorphism in the cyclooxygenase-2 (COX-2) and presenilin 2 (PS2) gene promoters: impact on inflammatory signaling and potential contribution to the etiopathology of Alzheimer's disease (AD)

Author

Cui, J.G., primary, Mukherjee, P.K., additional, Thompson, H.W., additional, Prescott, S.M., additional, Carlson, M., additional, Sato, C., additional, Salehi-Rad, S., additional, Rogaeva, E., additional, St George-Hyslop, P., additional, Farrer, L.A., additional, Moliaka, Y., additional, Grigorenko, A., additional, Rogaev, E.I., additional, Bazan, N.G., additional, and Lukiw, W.J., additional

Published
2004
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143. Screening for PS1 mutations in a referral-based series of AD cases: 21 Novel mutations

Author

Rogaeva, E. A., primary, Fafel, K.C., additional, Song, Y.Q., additional, Medeiros, H., additional, Sato, C., additional, Liang, Y., additional, Richard, E., additional, Rogaev, E.I., additional, Frommelt, P., additional, Sadovnick, A. D., additional, Meschino, W., additional, Rockwood, K., additional, Boss, M. A., additional, Mayeux, R., additional, and St. George-Hyslop, P., additional

Published
2001
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144. Nicastrin binds to membrane-tethered Notch

Author

Chen, Fusheng, primary, Yu, Gang, additional, Arawaka, Shigeki, additional, Nishimura, Masaki, additional, Kawarai, Toshitaka, additional, Yu, Haung, additional, Tandon, Anurag, additional, Supala, Agnes, additional, Song, You Qiang, additional, Rogaeva, Ekaterina, additional, Milman, Paul, additional, Sato, Christine, additional, Yu, Cong, additional, Janus, Christopher, additional, Lee, Julie, additional, Song, Lixin, additional, Zhang, Lili, additional, Fraser, Paul E., additional, and St George-Hyslop, P. H., additional

Published
2001
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145. Corticobasal degeneration and progressive supranuclear palsy share a common tau haplotype

Author

Houlden, H., primary, Baker, M., additional, Morris, H.R., additional, MacDonald, N., additional, Pickering-Brown, S., additional, Adamson, J., additional, Lees, A.J., additional, Rossor, M.N., additional, Quinn, N.P., additional, Kertesz, A., additional, Khan, M.N., additional, Hardy, J., additional, Lantos, P.L., additional, St. George-Hyslop, P., additional, Munoz, D.G., additional, Mann, D., additional, Lang, A.E., additional, Bergeron, C., additional, Bigio, E.H., additional, Litvan, I., additional, Bhatia, K.P., additional, Dickson, D., additional, Wood, N.W., additional, and Hutton, M., additional

Published
2001
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147. Improved Clinical Performance and Teamwork of Pediatric Interprofessional Resuscitation Teams With a Simulation-Based Educational Intervention*

Author

Gilfoyle, Elaine, Koot, Deanna A., Annear, John C., Bhanji, Farhan, Cheng, Adam, Duff, Jonathan P., Grant, Vincent J., St. George-Hyslop, Cecilia E., Delaloye, Nicole J., Kotsakis, Afrothite, McCoy, Carolyn D., Ramsay, Christa E., Weiss, Matthew J., and Gottesman, Ronald D.

Abstract

Supplemental Digital Content is available in the text.

Published
2017
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