@article{7c37ef3f32ad413f88fa753191aeac60,
title = "A potential endophenotype for Alzheimer's disease: cerebrospinal fluid clusterin",
abstract = "Genome-wide association studies have associated clusterin (CLU) variants with Alzheimer's disease (AD). However, the role of CLU on AD pathogenesis is not totally understood. We used cerebrospinal fluid (CSF) and plasma CLU levels as endophenotypes for genetic studies to understand the role of CLU in AD. CSF, but not plasma, CLU levels were significantly associated with AD status and CSF tau/amyloid-beta ratio, and highly correlated with CSF apolipoprotein E (APOE) levels. Several loci showed almost genome-wide significant associations including LINC00917 (p = 3.98 × 10−7) and interleukin 6 (IL6, p = 9.94 × 10−6, in the entire data set and in the APOE ε4- individuals p = 7.40 × 10−8). Gene ontology analyses suggest that CSF CLU levels may be associated with wound healing and immune response which supports previous functional studies that demonstrated an association between CLU and IL6. CLU may play a role in AD by influencing immune system changes that have been observed in AD or by disrupting healing after neurodegeneration.",
keywords = "APOE, Alzheimer's disease, Cerebrospinal fluid, Clusterin, Gene ontology, Immune response",
author = "Yuetiva Deming and Jian Xia and Yefei Cai and Jenny Lord and Peter Holmans and Sarah Bertelsen and David Holtzman and Morris, {John C.} and Kelly Bales and Pickering, {Eve H.} and John Kauwe and Alison Goate and Carlos Cruchaga",
note = "Funding Information: This work was supported by Pfizer and grants from the National Institutes of Health ( R01-AG044546 , P01-AG003991 ), and the Alzheimer's Association ( NIRG-11–200110 ). This research was conducted while Carlos Cruchaga was a recipient of a New Investigator Award in Alzheimer's disease from the American Federation for Aging Research . Carlos Cruchaga is a recipient of a BrightFocus Foundation Alzheimer's Disease Research Grant ( A2013359S ). The recruitment and clinical characterization of research participants at Washington University were supported by NIH P50 AG05681 , P01 AG03991 , and P01 AG026276 . Some of the samples used in this study were genotyped by the ADGC and GERAD. ADGC is supported by grants from the NIH (# U01AG032984 ) and GERAD from the Wellcome Trust ( GR082604MA ) and the Medical Research Council ( G0300429 ). Data collection and sharing for this project was funded by the Alzheimer's Disease Neuroimaging Initiative (ADNI) ( National Institutes of Health Grant U01 AG024904 ) and DOD ADNI (Department of Defense award number W81XWH-12-2-0012 ). ADNI is funded by the National Institute on Aging , the National Institute of Biomedical Imaging and Bioengineering , and through generous contributions from the following: Alzheimer's Association ; Alzheimer's Drug Discovery Foundation ; Araclon Biotech ; BioClinica, Inc. ; Biogen Idec ; Bristol-Myers Squibb Company ; Eisai ; Elan Pharmaceuticals, Inc. ; Eli Lilly and Company ; EuroImmun ; F. Hoffmann-La Roche Ltd. and its affiliated company Genentech, Inc. ; Fujirebio ; GE Healthcare ; IXICO Ltd. ; Janssen Alzheimer Immunotherapy Research & Development, LLC ; Johnson & Johnson Pharmaceutical Research & Development LLC ; Medpace ; Merck ; Meso Scale Diagnostics, LLC. ; NeuroRx Research ; Neurotrack Technologies ; Novartis Pharmaceuticals Corporation ; Pfizer Inc. ; Piramal Imaging ; Servier ; Synarc Inc. ; and Takeda Pharmaceutical Company . The Canadian Institutes of Rev December 5, 2013 Health Research is providing funds to support ADNI clinical sites in Canada. Private sector contributions are facilitated by the Foundation for the National Institutes of Health ( www.fnih.org ). The grantee organization is the Northern California Institute for Research and Education, and the study is coordinated by the Alzheimer's Disease Cooperative Study at the University of California, San Diego. ADNI data are disseminated by the Laboratory for Neuro Imaging at the University of Southern California. Publisher Copyright: {\textcopyright} 2016 Elsevier Inc.",
year = "2016",
month = jan,
day = "1",
doi = "10.1016/j.neurobiolaging.2015.09.009",
language = "English",
volume = "37",
pages = "208.e1--208.e9",
journal = "Neurobiology of Aging",
issn = "0197-4580",
}