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.
- Froelich, L.
- Huell, M.
- Buscemi, L.
- Herms, S.
- Koelsch, H.
- Scheltens, P.
- Breteler, M.M.
- Ruether, E.
- Wiltfang, J.
- Goate, A.
- Jessen, F.
- Maier, W.
- Heneka, M.T.
- Becker, T.
- Noethen, M.M.
DOIAbstract
Cerebrospinal fluid amyloid-beta 1-42 (Abeta1-42) 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 Abeta1-42 and pTau181 in AD dementia patients followed by independent replication. An association was found between Abeta1-42 level and a single-nucleotide polymorphism in SUCLG2 (rs62256378) (P = 2.5x10(-12)). An interaction between APOE genotype and rs62256378 was detected (P = 9.5 x 10(-5)), with the strongest effect being observed in APOE-epsilon4 noncarriers. Clinically, rs62256378 was associated with rate of cognitive decline in AD dementia patients (P = 3.1 x 10(-3)). Functional microglia experiments showed t...
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