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Title | SUCLG2 identified as both a determinator of CSF Aβ1-42 levels and an attenuator of cognitive decline in Alzheimer's disease. |
Publication Type | Journal Article |
Year of Publication | 2014 |
Authors | Ramirez A, van der Flier WM, Herold C, Ramonet D, Heilmann S, Lewczuk P, Popp J, Lacour A, Drichel D, Louwersheimer E, Kummer MP, Cruchaga C, Hoffmann P, Teunissen C, Holstege H, Kornhuber J, Peters O, Naj AC, Chouraki V, Bellenguez C, Gerrish A, Heun R, Frölich L, Hüll M, Buscemi L, Herms S, Kölsch H, Scheltens P, Breteler MM, Rüther E, Wiltfang J, Goate A, Jessen F, Maier W, Heneka MT, Becker T, Nöthen MM |
Corporate Authors | International Genomics of Alzheimer's Project(IGAP), Alzheimer's Disease Neuroimaging Initiative(ADNI) |
Journal | Hum Mol Genet |
Volume | 23 |
Issue | 24 |
Pagination | 6644-58 |
Date Published | 2014 Dec 15 |
ISSN | 1460-2083 |
Keywords | Aged, Alzheimer Disease, Amyloid beta-Peptides, Apolipoprotein E4, Cognition, Female, Gene Expression Regulation, Genome-Wide Association Study, Humans, Male, Nuclear Proteins, Peptide Fragments, Phosphorylation, Polymorphism, Single Nucleotide, RNA-Binding Proteins, Serine-Arginine Splicing Factors, Signal Transduction, tau Proteins |
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. |
DOI | 10.1093/hmg/ddu372 |
Alternate Journal | Hum. Mol. Genet. |
PubMed ID | 25027320 |
PubMed Central ID | PMC4240204 |
Grant List | P30 AG010129 / AG / NIA NIH HHS / United States U24 AG021886 / AG / NIA NIH HHS / United States U01 AG032984 / AG / NIA NIH HHS / United States U01 AG024904 / AG / NIA NIH HHS / United States / / Canadian Institutes of Health Research / Canada K01 AG030514 / AG / NIA NIH HHS / United States |