Open AccessGPR39 localization in the aging human brain and correlation of expression and polymorphism with vascular cognitive impairment
Author(s) -
Davis Catherine M.,
Bah Thierno M.,
Zhang Wenri H.,
Nelson Jonathan W.,
Golgotiu Kirsti,
Nie Xiao,
Alkayed Farah N.,
Young Jennifer M.,
Woltjer Randy L.,
Silbert Lisa C.,
Grafe Marjorie R.,
Alkayed Nabil J.
Publication year - 2021
Publication title -
alzheimer's and dementia: translational research and clinical interventions
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.49
H-Index - 30
ISSN - 2352-8737
DOI - 10.1002/trc2.12214
Subject(s) - snp , single nucleotide polymorphism , white matter , prefrontal cortex , microglia , pathogenesis , hyperintensity , biomarker , human brain , pathology , medicine , biology , neuroscience , magnetic resonance imaging , cognition , genetics , genotype , gene , inflammation , radiology
Abstract Introduction The 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. Methods We performed GPR39 immunohistochemical analysis in post mortem brain samples from mild cognitive impairment (MCI) and control subjects. DNA was analyzed for GPR39 single nucleotide polymorphisms (SNPs), and correlated with white matter hyperintensity (WMH) burden on pre mortem magnetic resonance imaging. Results GPR39 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 wild‐type or heterozygous SNP carriers. Discussion GPR39 may play a role in aging‐related VCI, and may serve as a therapeutic target and biomarker for the risk of developing VCI.