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

Ramirez, A.; van der Flier, W.M.; Herold, C.; Ramonet, D.; Heilmann, S.; Lewczuk, P.; Popp, J.; Lacour, A.; Drichel, D.; Louwersheimer, E.; Kummer, M.P.; Cruchaga, C.; Hoffmann, P.; Teunissen, C.; Holstege, H.; Kornhuber, J.; Peters, O.; Naj, A.C.; Chouraki, V.; Bellenguez, C.; Gerrish, A.; Heun, R.; Heun, R.; Frölich, L.; Hüll, M.; Buscemi, L.; Herms, S.; Kölsch, H.; Scheltens, P.; Breteler, M.M.; Rüther, E.; Wiltfang, J.; Goate, A.; Jessen, F.; Maier, W.; Heneka, M.T.; Becker, T.; Nöthen, M.M.

doi:10.1093/hmg/ddu372

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

Details

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State: Public
Version: author

Serval ID

serval:BIB_05087FA7722D

Type

Article: article from journal or magazin.

Collection

Publications

Institution

UNIL/CHUV

Title

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

Journal

Human Molecular Genetics

Author(s)

Ramirez A., van der Flier W.M., Herold C., Ramonet D., Heilmann S., Lewczuk P., Popp J., Lacour A., Drichel D., Louwersheimer E., Kummer M.P., Cruchaga C., Hoffmann P., Teunissen C., Holstege H., Kornhuber J., Peters O., Naj A.C., Chouraki V., Bellenguez C., Gerrish A., Heun R., Heun R., Frölich L., Hüll M., Buscemi L., Herms S., Kölsch H., Scheltens P., Breteler M.M., Rüther E., Wiltfang J., Goate A., Jessen F., Maier W., Heneka M.T., Becker T., Nöthen M.M.

Working group(s)

International Genomics of Alzheimer's Project (IGAP), Alzheimer's Disease Neuroimaging Initiative (ADNI)

ISSN

1460-2083 (Electronic)

ISSN-L

0964-6906

Publication state

Published

Issued date

2014

Peer-reviewed

Oui

Volume

Number

Pages

6644-6658

Language

english

Notes

Publication types: Journal ArticlePublication Status: ppublish

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.

URN

urn:nbn:ch:serval-BIB_05087FA7722D5

OAI-PMH

oai:serval.unil.ch:BIB_05087FA7722D

DOI

10.1093/hmg/ddu372

Pubmed

25027320

Web of science

000347921900019

Open Access

Yes