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GWAS Study

A potential endophenotype for Alzheimer's disease: cerebrospinal fluid clusterin.

Deming Y, Xia J, Cai Y et al.

26545630 PubMed ID
GWAS Study Type
673 Participants
43 Views
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Chapter I

Publication Details

Comprehensive information about this research publication

Authors

DY
Deming Y
XJ
Xia J
CY
Cai Y
LJ
Lord J
HP
Holmans P
BS
Bertelsen S
HD
Holtzman D
MJ
Morris JC
BK
Bales K
PE
Pickering EH
KJ
Kauwe J
GA
Goate A
CC
Cruchaga C
Chapter II

Abstract

Summary of the research findings

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.

300 Alzheimer's disease cases, 373 controls

Chapter III

Study Statistics

Key metrics and study information

673
Total Participants
GWAS
Study Type
No
Replicated
U.S.
Recruitment Country
Chapter IV

AI-Generated Summary

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