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 WM, Herold C, Ramonet D, Heilmann S, Lewczuk P, Popp J, Lacour A, Drichel D, Louwersheimer E, Kummer MP, Cruchaga C, Hoffmann P, Teunissen C, Holstege H, Kornhuber J, Peters O, Naj AC, Chouraki V, Bellenguez C, Gerrish A, Heun R, Froelich L, Huell M, Buscemi L, Herms S, Koelsch H, Scheltens P, Breteler MM, Ruether E, Wiltfang J, Goate A, Jessen F, Maier W, Heneka MT, Becker T, Noethen MM (2014)

Publication Type: Journal article

Publication year: 2014

Journal

Human Molecular Genetics Oxford University Press (OUP): Policy B - Oxford Open Option B

Publisher: Oxford University Press (OUP): Policy B - Oxford Open Option B

Book Volume: 23

Pages Range: 6644-58

Journal Issue: 24

DOI: 10.1093/hmg/ddu372

Abstract

Cerebrospinal fluid amyloid-beta 1-42 (A?1-42) 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 A?1-42 and pTau181 in AD dementia patients followed by independent replication. An association was found between A?1-42 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-?4 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 A?1-42.

Authors with CRIS profile

Piotr Lewczuk Department of Psychiatry and Psychotherapy Johannes Kornhuber Lehrstuhl für Psychiatrie und Psychotherapie

Involved external institutions

Rheinische Friedrich-Wilhelms-Universität Bonn DE Germany (DE) Vrije Universiteit Amsterdam (VU) / University Amsterdam NL Netherlands (NL) Deutsches Zentrum für Neurodegenerative Erkrankungen (DZNE) DE Germany (DE) Washington University US United States (USA) (US) Charité - Universitätsmedizin Berlin DE Germany (DE) University of Pennsylvania US United States (USA) (US) Boston University US United States (USA) (US) National Institute for Health and Medical Research / Institut national de la santé et de la recherche médicale (INSERM) FR France (FR) Cardiff University GB United Kingdom (GB) Ruprecht-Karls-Universität Heidelberg DE Germany (DE) Albert-Ludwigs-Universität Freiburg DE Germany (DE) Université de Lausanne (UNIL) CH Switzerland (CH) Georg-August-Universität Göttingen DE Germany (DE)

How to cite

APA:

Ramirez, A., Van Der Flier, W.M., Herold, C., Ramonet, D., Heilmann, S., Lewczuk, P.,... Noethen, 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), 6644-58. https://doi.org/10.1093/hmg/ddu372

MLA:

Ramirez, Alfredo, et al. "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 (2014): 6644-58.

BibTeX: Download