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

Article type: Short Communication

Authors: Sakae, Nobutaka^a | Heckman, Michael G.^{b; *} | Vargas, Emily R.^b | Carrasquillo, Minerva M.^a | Murray, Melissa E.^a | Kasanuki, Koji^a | Ertekin-Taner, Nilufer^{a; c} | Younkin, Steven G.^a | Dickson, Dennis W.^a

Affiliations: [a] Department of Neuroscience, Mayo Clinic, Jacksonville, FL, USA | [b] Division of Biomedical Statistics and Informatics, Mayo Clinic, Jacksonville, FL, USA | [c] Department of Neurology, Mayo Clinic, Jacksonville, FL, USA

Correspondence: [*] Correspondence to: Michael G. Heckman, MS, Division of Biomedical Statistics and Informatics, Mayo Clinic, 4500 San Pablo Road, Jacksonville, FL 32224, USA. Tel.: +1 904 953 1049; Fax: +1 904 953 0277; E-mail: [email protected].

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 ɛ4 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

DOI: 10.3233/JAD-190451

Journal: Journal of Alzheimer's Disease, vol. 70, no. 3, pp. 659-666, 2019