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

被引：48

作者：

Deming, Yuetiva ^{[1
]}

Xia, Jian ^{[1
]}

Cai, Yefei ^{[1
]}

Lord, Jenny ^{[1
]}

Holmans, Peter ^{[2
]}

Bertelsen, Sarah ^{[1
]}

Holtzman, David ^{[3
,4
,5
,6
]}

Morris, John C. ^{[3
,4
,5
,6
]}

Bales, Kelly ^{[7
]}

Pickering, Eve H. ^{[7
]}

Kauwe, John ^{[8
]}

Goate, Alison ^{[1
,5
,6
]}

Cruchaga, Carlos ^{[1
,6
]}

机构：

[1] Washington Univ, Sch Med, Dept Psychiat, St Louis, MO 63110 USA

[2] Cardiff Univ, Sch Med, MRC Ctr Neuropsychiat Genet & Genom, Inst Psychol Med & Clin Neurosci, Cardiff CF10 3AX, S Glam, Wales

[3] Washington Univ, Sch Med, Dept Neurol, St Louis, MO 63110 USA

[4] Washington Univ, Sch Med, Dept Dev Biol, St Louis, MO 63110 USA

[5] Washington Univ, Sch Med, Knight Alzheimers Dis Res Ctr, St Louis, MO 63110 USA

[6] Washington Univ, Sch Med, Hope Ctr Neurol Disorders, St Louis, MO 63110 USA

[7] Pfizer Inc, Worldwide Res & Dev, Neurosci Res Unit, Groton, CT 06340 USA

[8] Brigham Young Univ, Dept Biol, Provo, UT 84602 USA

来源：

NEUROBIOLOGY OF AGING | 2016年 / 37卷

基金：

美国国家卫生研究院; 英国医学研究理事会; 英国惠康基金;

关键词：

Alzheimer's disease; APOE; Clusterin; Cerebrospinal fluid; Gene ontology; Immune response; GENOME-WIDE ASSOCIATION; AMYLOID-BETA; IDENTIFIES VARIANTS; NUCLEAR CLUSTERIN; APOLIPOPROTEIN-J; GENE ONTOLOGY; INTERLEUKIN-6; EXPRESSION; DATABASE; PROTEIN;

D O I：

10.1016/j.neurobiolaging.2015.09.009

中图分类号：

R592 [老年病学]; C [社会科学总论];

学科分类号：

03 ; 0303 ; 100203 ;

摘要：

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 x 10(-7)) and interleukin 6 (IL6, p = 9.94 x 10(-6), in the entire data set and in the APOE epsilon 4- individuals p = 7.40 x 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. (C) 2016 Elsevier Inc. All rights reserved.

引用

页码：208.e1 / 208.e9

页数：9

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