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

TitleSUCLG2 identified as both a determinator of CSF Aβ1-42 levels and an attenuator of cognitive decline in Alzheimer's disease.
Publication TypeJournal Article
Year of Publication2014
AuthorsRamirez 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 AuthorsInternational Genomics of Alzheimer's Project(IGAP), Alzheimer's Disease Neuroimaging Initiative(ADNI)
JournalHum Mol Genet
Volume23
Issue24
Pagination6644-58
Date Published2014 Dec 15
ISSN1460-2083
KeywordsAged, 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.

DOI10.1093/hmg/ddu372
Alternate JournalHum. Mol. Genet.
PubMed ID25027320
PubMed Central IDPMC4240204
Grant ListP30 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