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SUCLG2 identified as both a determinator of CSF A 1-42 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, Amy, Heun, R., Frolich, L., Hull, M., Buscemi, L., Herms, S., Kolsch, H., Scheltens, P., Breteler, M. M., Ruther, E., Wiltfang, J., Goate, A., Jessen, F., Maier, W., Heneka, M. T., Becker, T. and Nothen, M. M. 2014. SUCLG2 identified as both a determinator of CSF A 1-42 levels and an attenuator of cognitive decline in Alzheimer's disease. Human Molecular Genetics 23 (24) , pp. 6644-6658. 10.1093/hmg/ddu372

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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.

Item Type: Article
Date Type: Published Online
Status: Published
Schools: MRC Centre for Neuropsychiatric Genetics and Genomics (CNGG)
Medicine
Subjects: R Medicine > R Medicine (General)
ISSN: 0964-6906
Last Modified: 14 Mar 2019 11:40
URI: https://orca.cardiff.ac.uk/id/eprint/74873

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