TY - JOUR
T1 - SUCLG2 identified as both a determinator of CSF Aβ1-42 levels and an attenuator of cognitive decline in Alzheimer's disease
AU - International Genomics of Alzheimer's Project (IGAP)
AU - Alzheimer's Disease Neuroimaging Initiative (ADNI)
AU - Ramirez, Alfredo
AU - van der Flier, Wiesje M.
AU - Herold, Christine
AU - Ramonet, David
AU - Heilmann, Stefanie
AU - Lewczuk, Piotr
AU - Popp, Julius
AU - Lacour, André
AU - Drichel, Dmitriy
AU - Louwersheimer, Eva
AU - Kummer, Markus P.
AU - Cruchaga, Carlos
AU - Hoffmann, Per
AU - Teunissen, Charlotte
AU - Holstege, Henne
AU - Kornhuber, Johannes
AU - Peters, Oliver
AU - Naj, Adam C.
AU - Chouraki, Vincent
AU - Bellenguez, Céline
AU - Gerrish, Amy
AU - Heun, Reiner
AU - Frölich, Lutz
AU - Hüll, Michael
AU - Buscemi, Lara
AU - Herms, Stefan
AU - Kölsch, Heike
AU - Scheltens, Philip
AU - Breteler, Monique M.
AU - Rüther, Eckart
AU - Wiltfang, Jens
AU - Goate, Alison
AU - Jessen, Frank
AU - Maier, Wolfgang
AU - Heneka, Michael T.
AU - Becker, Tim
AU - Nöthen, Markus M.
N1 - Publisher Copyright:
© The Author 2014. Published by Oxford University Press. All rights reserved. For Permissions, please email: [email protected].
PY - 2014/12/15
Y1 - 2014/12/15
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=84969298076&partnerID=8YFLogxK
U2 - 10.1093/hmg/ddu372
DO - 10.1093/hmg/ddu372
M3 - Article
C2 - 25027320
AN - SCOPUS:84969298076
SN - 0964-6906
VL - 23
SP - 6644
EP - 6658
JO - Human molecular genetics
JF - Human molecular genetics
IS - 24
ER -