Evaluation of Associations of Alzheimer's Disease Risk Variants that Are Highly Expressed in Microglia with Neuropathological Outcome Measures

Nobutaka Sakae; Michael G. Heckman; Emily R. Vargas; Minerva M. Carrasquillo; Melissa E. Murray; Koji Kasanuki; Nilufer Ertekin-Taner; Steven G. Younkin; Dennis W. Dickson

doi:10.3233/JAD-190451

Evaluation of Associations of Alzheimer's Disease Risk Variants that Are Highly Expressed in Microglia with Neuropathological Outcome Measures

Nobutaka Sakae, Michael G. Heckman, Emily R. Vargas, Minerva M. Carrasquillo, Melissa E. Murray, Koji Kasanuki, Nilufer Ertekin-Taner, Steven G. Younkin, Dennis W. Dickson

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3 Scopus citations

Abstract

A number of Alzheimer's disease (AD) susceptibility loci are expressed abundantly in microglia. We examined associations between AD risk variants in genes that are highly expressed in microglia and neuropathological outcomes, including cerebral amyloid angiopathy (CAA) and microglial activation, in 93 AD patients. We observed significant associations of CAA pathology with APOE ϵ4 and PTK2B rs28834970. Nominally significant associations with measures of microglial activation in white matter were observed for variants in PTK2B, PICALM, and CR1. Our findings suggest that several AD risk variants may also function as disease modifiers through amyloid-β metabolism and white matter microglial activity.

Original language	English (US)
Pages (from-to)	659-666
Number of pages	8
Journal	Journal of Alzheimer's Disease
Volume	70
Issue number	3
DOIs	https://doi.org/10.3233/JAD-190451
State	Published - 2019

Keywords

Alzheimer's disease
Genome-wide association study
Microglia
Neuropathology
Risk variant

ASJC Scopus subject areas

Neuroscience(all)
Clinical Psychology
Geriatrics and Gerontology
Psychiatry and Mental health

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10.3233/JAD-190451

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Sakae, N., Heckman, M. G., Vargas, E. R., Carrasquillo, M. M., Murray, M. E., Kasanuki, K., Ertekin-Taner, N., Younkin, S. G., & Dickson, D. W. (2019). Evaluation of Associations of Alzheimer's Disease Risk Variants that Are Highly Expressed in Microglia with Neuropathological Outcome Measures. Journal of Alzheimer's Disease, 70(3), 659-666. https://doi.org/10.3233/JAD-190451

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title = "Evaluation of Associations of Alzheimer's Disease Risk Variants that Are Highly Expressed in Microglia with Neuropathological Outcome Measures",

abstract = "A number of Alzheimer's disease (AD) susceptibility loci are expressed abundantly in microglia. We examined associations between AD risk variants in genes that are highly expressed in microglia and neuropathological outcomes, including cerebral amyloid angiopathy (CAA) and microglial activation, in 93 AD patients. We observed significant associations of CAA pathology with APOE ϵ4 and PTK2B rs28834970. Nominally significant associations with measures of microglial activation in white matter were observed for variants in PTK2B, PICALM, and CR1. Our findings suggest that several AD risk variants may also function as disease modifiers through amyloid-β metabolism and white matter microglial activity.",

keywords = "Alzheimer's disease, Genome-wide association study, Microglia, Neuropathology, Risk variant",

author = "Nobutaka Sakae and Heckman, {Michael G.} and Vargas, {Emily R.} and Carrasquillo, {Minerva M.} and Murray, {Melissa E.} and Koji Kasanuki and Nilufer Ertekin-Taner and Younkin, {Steven G.} and Dickson, {Dennis W.}",

note = "Funding Information: Support by the Robert E. Jacoby Professorship of Alzheimer's Research and Mayo Clinic Alzheimer Disease Research Center (P50 AG16574) Publisher Copyright: {\textcopyright} 2019 - IOS Press and the authors. All rights reserved.",

year = "2019",

doi = "10.3233/JAD-190451",

language = "English (US)",

volume = "70",

pages = "659--666",

journal = "Journal of Alzheimer's Disease",

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AU - Sakae, Nobutaka

AU - Heckman, Michael G.

AU - Vargas, Emily R.

AU - Carrasquillo, Minerva M.

AU - Murray, Melissa E.

AU - Kasanuki, Koji

AU - Ertekin-Taner, Nilufer

AU - Younkin, Steven G.

AU - Dickson, Dennis W.

N1 - Funding Information: Support by the Robert E. Jacoby Professorship of Alzheimer's Research and Mayo Clinic Alzheimer Disease Research Center (P50 AG16574) Publisher Copyright: © 2019 - IOS Press and the authors. All rights reserved.

PY - 2019

Y1 - 2019

N2 - A number of Alzheimer's disease (AD) susceptibility loci are expressed abundantly in microglia. We examined associations between AD risk variants in genes that are highly expressed in microglia and neuropathological outcomes, including cerebral amyloid angiopathy (CAA) and microglial activation, in 93 AD patients. We observed significant associations of CAA pathology with APOE ϵ4 and PTK2B rs28834970. Nominally significant associations with measures of microglial activation in white matter were observed for variants in PTK2B, PICALM, and CR1. Our findings suggest that several AD risk variants may also function as disease modifiers through amyloid-β metabolism and white matter microglial activity.

AB - A number of Alzheimer's disease (AD) susceptibility loci are expressed abundantly in microglia. We examined associations between AD risk variants in genes that are highly expressed in microglia and neuropathological outcomes, including cerebral amyloid angiopathy (CAA) and microglial activation, in 93 AD patients. We observed significant associations of CAA pathology with APOE ϵ4 and PTK2B rs28834970. Nominally significant associations with measures of microglial activation in white matter were observed for variants in PTK2B, PICALM, and CR1. Our findings suggest that several AD risk variants may also function as disease modifiers through amyloid-β metabolism and white matter microglial activity.

KW - Alzheimer's disease

KW - Genome-wide association study

KW - Microglia

KW - Neuropathology

KW - Risk variant

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Evaluation of Associations of Alzheimer's Disease Risk Variants that Are Highly Expressed in Microglia with Neuropathological Outcome Measures

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