SUCLG2 identified as both a determinator of CSF Aβ1-42 levels and an attenuator of cognitive decline in Alzheimer's disease
Ramirez, Alfredo ; van der Flier, Wiesje M. ; Herold, Christine ; Ramonet, David ; Heilmann, Stefanie ; Lewczuk, Piotr ; Popp, Julius ; Lacour, André ; Drichel, Dmitriy ; Louwersheimer, Eva ; Kummer, Markus P. ; Cruchaga, Carlos ; Hoffmann, Per ; Teunissen, Charlotte ; Holstege, Henne ; Kornhuber, Johannes ; Peters, Oliver ; Naj, Adam C. ; Chouraki, Vincent ; Bellenguez, Céline ; Gerrish, Amy ; Heun, Reiner ; Frölich, Lutz ; Hüll, Michael ; Buscemi, Lara ; Herms, Stefan ; Kölsch, Heike ; Scheltens, Philip ; Breteler, Monique M. ; Rüther, Eckart ; Wiltfang, Jens ; Goate, Alison ; Jessen, Frank ; Maier, Wolfgang ; Heneka, Michael T. ; Becker, Tim ; Nöthen, Markus M.
In: Human Molecular Genetics, 2014, vol. 23, no. 24, p. 6644-6658
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- 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