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

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. © The Author 2014. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

Citation

Alfredo Ramirez, Wiesje M van der Flier, Christine Herold, David Ramonet, Stefanie Heilmann, Piotr Lewczuk, Julius Popp, André Lacour, Dmitriy Drichel, Eva Louwersheimer, Markus P Kummer, Carlos Cruchaga, Per Hoffmann, Charlotte Teunissen, Henne Holstege, Johannes Kornhuber, Oliver Peters, Adam C Naj, Vincent Chouraki, Céline Bellenguez, Amy Gerrish, International Genomics of Alzheimer's Project (IGAP), Alzheimer's Disease Neuroimaging Initiative (ADNI), Reiner Heun, Lutz Frölich, Michael Hüll, Lara Buscemi, Stefan Herms, Heike Kölsch, Philip Scheltens, Monique M Breteler, Eckart Rüther, Jens Wiltfang, Alison Goate, Frank Jessen, Wolfgang Maier, Michael T Heneka, Tim Becker, Markus M Nöthen. SUCLG2 identified as both a determinator of CSF Aβ1-42 levels and an attenuator of cognitive decline in Alzheimer's disease. Human molecular genetics. 2014 Dec 15;23(24):6644-58

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PMID: 25027320

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