GPR39 Localization in Aging Human Brain and Correlation of Expression and Polymorphism with Vascular Cognitive Impairment

Abstract

INTRODUCTIONThe pathogenesis of vascular cognitive impairment (VCI) is not fully understood. GPR39, an orphan G-protein coupled receptor, is implicated in neurological disorders but its role in VCI is unknown. METHODSWe performed GPR39 immunohistochemical analysis in postmortem brain samples from mild cognitive impairment (MCI) and control subjects. DNA was analyzed for GPR39 SNPs, and correlated with white matter hyperintensity (WMH) burden on premortem MRI. RESULTSGPR39 is expressed in aged human dorsolateral prefrontal cortex, localized to microglia and peri-capillary cells resembling pericytes. GPR39-capillary colocalization, and density of GPR39-expressing microglia was increased in aged brains compared to young. SNP distribution was equivalent between groups; however, homozygous SNP carriers were present only in the MCI group, and had higher WMH volume than WT or heterozygous SNP carriers. DISCUSSIONGPR39 may play a role in aging-related VCI, and may serve as a therapeutic target and biomarker for the risk of developing VCI.