| Literature DB >> 26545630 |
Yuetiva Deming1, Jian Xia1, Yefei Cai1, Jenny Lord1, Peter Holmans2, Sarah Bertelsen1, David Holtzman3, John C Morris3, Kelly Bales4, Eve H Pickering4, John Kauwe5, Alison Goate6, Carlos Cruchaga7.
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.Entities:
Keywords: APOE; Alzheimer's disease; Cerebrospinal fluid; Clusterin; Gene ontology; Immune response
Mesh：
Substances：
Year: 2015 PMID： 26545630 PMCID： PMC5118651 DOI： 10.1016/j.neurobiolaging.2015.09.009
Source DB: PubMed Journal: Neurobiol Aging ISSN： 0197-4580 Impact factor: 4.673