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

Research output: Contribution to journalArticle

2 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 languageEnglish (US)
Pages (from-to)659-666
Number of pages8
JournalJournal of Alzheimer's Disease
Volume70
Issue number3
DOIs
StatePublished - Jan 1 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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