Genetic susceptibility for Alzheimer disease neuritic plaque pathology.
Genetic susceptibility for Alzheimer disease neuritic plaque pathology.
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DOI：
10.1001/jamaneurol.2013.2815
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发表时间：
2013-09-01
期刊：
影响因子：
29
通讯作者：
Bennett, David A.
中科院分区：
文献类型：
--
作者：
Shulman, Joshua M.;Chen, Kewei;Keenan, Brendan T.;Chibnik, Lori B.;Fleisher, Adam;Thiyyagura, Pradeep;Roontiva, Auttawut;McCabe, Cristin;Patsopoulos, Nikolaos A.;Corneveaux, Jason J.;Yu, Lei;Huentelman, Matthew J.;Evans, Denis A.;Schneider, Julie A.;Reiman, Eric M.;De Jager, Philip L.;Bennett, David A.
To investigate whether Alzheimer’s disease (AD) susceptibility loci from genome-wide association studies (GWAS) impact neuritic plaque pathology and to additionally identify novel risk loci for this trait. Candidate analysis of single nucleotide polymorphisms (SNPs) and GWAS in a joint clinicopathologic cohort study, followed by targeted validation in independent neuroimaging cohorts. 725 deceased subjects from the Religious Orders and Rush Memory and Aging Project, two prospective, community-based studies of aging; the validation neuroimaging cohort consisted of 114 subjects from multiple clinical and research centers. A quantitative measure of neuritic plaque pathologic burden, based on assessments of silver-stained tissue averaged from multiple brain regions. Validation based on β-amyloid load by immunocytochemistry, and replication with fibrillar β-amyloid Positron Emission Tomography (PET) imaging with Pittsburgh Compound B or florbetapir. Besides the previously reported APOE and CR1 loci, we find that ABCA7 (rs3764650, P=0.02) and CD2AP (rs9349407, P=0.03) AD susceptibility loci are associated with neuritic plaque burden. In addition, among the top results of our GWAS, we discovered a novel variant near the amyloid precursor protein gene (APP, rs2829887) that is associated with neuritic plaques (P=3.3×10−6). This polymorphism was associated with postmortem β-amyloid load, as well as fibrillar β-amyloid in two independent cohorts of adults with normal cognition. These findings enhance understanding of AD risk factors by relating validated susceptibility alleles to increased neuritic plaque pathology and implicate common genetic variation at the APP locus in the earliest, pre-symptomatic stages of AD.
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影响因子：
30.8
作者：
Harold, Denise;Abraham, Richard;Hollingworth, Paul;Sims, Rebecca;Gerrish, Amy;Hamshere, Marian L.;Pahwa, Jaspreet Singh;Moskvina, Valentina;Dowzell, Kimberley;Williams, Amy;Jones, Nicola;Thomas, Charlene;Stretton, Alexandra;Morgan, Angharad R.;Lovestone, Simon;Powell, John;Proitsi, Petroula;Lupton, Michelle K.;Brayne, Carol;Rubinsztein, David C.;Gill, Michael;Lawlor, Brian;Lynch, Aoibhinn;Morgan, Kevin;Brown, Kristelle S.;Passmore, Peter A.;Craig, David;McGuinness, Bernadette;Todd, Stephen;Holmes, Clive;Mann, David;Smith, A. David;Love, Seth;Kehoe, Patrick G.;Hardy, John;Mead, Simon;Fox, Nick;Rossor, Martin;Collinge, John;Maier, Wolfgang;Jessen, Frank;Schuermann, Britta;van den Bussche, Hendrik;Heuser, Isabella;Kornhuber, Johannes;Wiltfang, Jens;Dichgans, Martin;Froelich, Lutz;Hampel, Harald;Huell, Michael;Rujescu, Dan;Goate, Alison M.;Kauwe, John S. K.;Cruchaga, Carlos;Nowotny, Petra;Morris, John C.;Mayo, Kevin;Sleegers, Kristel;Bettens, Karolien;Engelborghs, Sebastiaan;De Deyn, Peter P.;Van Broeckhoven, Christine;Livingston, Gill;Bass, Nicholas J.;Gurling, Hugh;McQuillin, Andrew;Gwilliam, Rhian;Deloukas, Panagiotis;Al-Chalabi, Ammar;Shaw, Christopher E.;Tsolaki, Magda;Singleton, Andrew B.;Guerreiro, Rita;Muehleisen, Thomas W.;Noethen, Markus M.;Moebus, Susanne;Joeckel, Karl-Heinz;Klopp, Norman;Wichmann, H-Erich;Carrasquillo, Minerva M.;Pankratz, V. Shane;Younkin, Steven G.;Holmans, Peter A.;O'Donovan, Michael;Owen, Michael J.;Williams, Julie
通讯作者：
Williams, Julie
影响因子：
11.2
作者：
Chibnik, Lori B.;Shulman, Joshua M.;Leurgans, Sue E.;Schneider, Julie A.;Wilson, Robert S.;Tran, Dong;Aubin, Cristin;Buchman, Aron S.;Heward, Christopher B.;Myers, Amanda J.;Hardy, John A.;Huentelman, Matthew J.;Corneveaux, Jason J.;Reiman, Eric M.;Evans, Denis A.;Bennett, David A.;De Jager, Philip L.
通讯作者：
De Jager, Philip L.
影响因子：
11
作者：
Bennett, DA;Schneider, JA;Arnold, SE
通讯作者：
Arnold, SE
影响因子：
--
作者：
Athan, ES;Lee, JH;Tycko, B
通讯作者：
Tycko, B
影响因子：
30.8
作者：
通讯作者：
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