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

Yuetiva Deming; Jian Xia; Yefei Cai; Jenny Lord; Peter Holmans; Sarah Bertelsen; David Holtzman; John C. Morris; Kelly Bales; Eve H. Pickering; John Kauwe; Alison Goate; Carlos Cruchaga

doi:10.1016/j.neurobiolaging.2015.09.009

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

Yuetiva Deming, Jian Xia, Yefei Cai, Jenny Lord, Peter Holmans, Sarah Bertelsen, David Holtzman, John C. Morris, Kelly Bales, Eve H. Pickering, John Kauwe, Alison Goate, Carlos Cruchaga

Research output: Contribution to journal › Article › peer-review

48 Scopus citations

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.

Original language	English
Pages (from-to)	208.e1-208.e9
Journal	Neurobiology of Aging
Volume	37
DOIs	https://doi.org/10.1016/j.neurobiolaging.2015.09.009
State	Published - 1 Jan 2016
Externally published	Yes

Keywords

APOE
Alzheimer's disease
Cerebrospinal fluid
Clusterin
Gene ontology
Immune response

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10.1016/j.neurobiolaging.2015.09.009

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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.",

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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",

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doi = "10.1016/j.neurobiolaging.2015.09.009",

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T2 - cerebrospinal fluid clusterin

AU - Deming, Yuetiva

AU - Xia, Jian

AU - Cai, Yefei

AU - Lord, Jenny

AU - Holmans, Peter

AU - Bertelsen, Sarah

AU - Holtzman, David

AU - Morris, John C.

AU - Bales, Kelly

AU - Pickering, Eve H.

AU - Kauwe, John

AU - Goate, Alison

AU - Cruchaga, Carlos

PY - 2016/1/1

Y1 - 2016/1/1

N2 - 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.

AB - 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.

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KW - Cerebrospinal fluid

KW - Clusterin

KW - Gene ontology

KW - Immune response

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ER -

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

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Keywords

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