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SUCLG2 identified as both a determinator of CSF Aβ1-42 levels and an attenuator of cognitive decline in Alzheimer's disease

Item Type:Article
Title:SUCLG2 identified as both a determinator of CSF Aβ1-42 levels and an attenuator of cognitive decline in Alzheimer's disease
Creators Name:Ramirez, A. and van der Flier, W.M. and Herold, C. and Ramonet, D. and Heilmann, S. and Lewczuk, P. and Popp, J. and Lacour, A. and Drichel, D. and Louwersheimer, E. and Kummer, M.P. and Cruchaga, C. and Hoffmann, P. and Teunissen, C. and Holstege, H. and Kornhuber, J. and Peters, O. and Naj, A.C. and Chouraki, V. and Bellenguez, C. and Gerrish, A. and Heun, R. and Froelich, L. and Huell, M. and Buscemi, L. and Herms, S. and Koelsch, H. and Scheltens, P. and Breteler, M.M. and Ruether, E. and Wiltfang, J. and Goate, A. and Jessen, F. and Maier, W. and Heneka, M.T. and Becker, T. and Noethen, M.M.
Abstract:Cerebrospinal fluid amyloid-beta 1-42 (Abeta1-42) 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 Abeta1-42 and pTau181 in AD dementia patients followed by independent replication. An association was found between Abeta1-42 level and a single-nucleotide polymorphism in SUCLG2 (rs62256378) (P = 2.5x10(-12)). An interaction between APOE genotype and rs62256378 was detected (P = 9.5 x 10(-5)), with the strongest effect being observed in APOE-epsilon4 noncarriers. Clinically, rs62256378 was associated with rate of cognitive decline in AD dementia patients (P = 3.1 x 10(-3)). Functional microglia experiments showed that SUCLG2 was involved in clearance of Abeta1-42.
Keywords:Alzheimer Disease, Amyloid beta-Peptides, Apolipoprotein E4, Cognition, Gene Expression Regulation, Genome-Wide Association Study, Nuclear Proteins, Peptide Fragments, Phosphorylation, RNA-Binding Proteins, Signal Transduction, Single Nucleotide Polymorphism, tau Proteins
Source:Human Molecular Genetics
ISSN:0964-6906
Publisher:Oxford University Press (U.K.)
Volume:23
Number:24
Page Range:6644-6658
Date:15 December 2014
Official Publication:https://doi.org/10.1093/hmg/ddu372
PubMed:View item in PubMed

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