| Literature DB >> 25027320 |
Alfredo Ramirez1, Wiesje M van der Flier2, Christine Herold3, David Ramonet4, Stefanie Heilmann5, Piotr Lewczuk6, Julius Popp7, André Lacour3, Dmitriy Drichel3, Eva Louwersheimer2, Markus P Kummer8, Carlos Cruchaga9, Per Hoffmann10, Charlotte Teunissen2, Henne Holstege2, Johannes Kornhuber6, Oliver Peters11, Adam C Naj12, Vincent Chouraki13, Céline Bellenguez14, Amy Gerrish15, Reiner Heun7, Lutz Frölich16, Michael Hüll17, Lara Buscemi18, Stefan Herms10, Heike Kölsch7, Philip Scheltens2, Monique M Breteler3, Eckart Rüther19, Jens Wiltfang19, Alison Goate20, Frank Jessen21, Wolfgang Maier21, Michael T Heneka8, Tim Becker22, Markus M Nöthen5.
Abstract
Cerebrospinal fluid amyloid-beta 1-42 (Aβ1-42) and phosphorylated Tau at position 181 (pTau181) are biomarkers of Alzheimer's disease (AD). We performed an analysis and meta-analysis of genome-wide association study data on Aβ1-42 and pTau181 in AD dementia patients followed by independent replication. An association was found between Aβ1-42 level and a single-nucleotide polymorphism in SUCLG2 (rs62256378) (P = 2.5×10(-12)). An interaction between APOE genotype and rs62256378 was detected (P = 9.5 × 10(-5)), with the strongest effect being observed in APOE-ε4 noncarriers. Clinically, rs62256378 was associated with rate of cognitive decline in AD dementia patients (P = 3.1 × 10(-3)). Functional microglia experiments showed that SUCLG2 was involved in clearance of Aβ1-42.Entities:
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Year: 2014 PMID： 25027320 PMCID： PMC4240204 DOI： 10.1093/hmg/ddu372
Source DB: PubMed Journal: Hum Mol Genet ISSN： 0964-6906 Impact factor: 6.150