Key result
Homozygous GPR39 SNPs are linked to MCI and greater white matter hyperintensity volume.
Why the study?
The pathogenesis of vascular cognitive impairment is not fully understood and the role of GPR39 in VCI is unknown.
Observational
GPR39 expression is altered in the aging human brain, and its polymorphisms correlate with white matter hyperintensity burden, suggesting a potential role in vascular cognitive impairment.
Answers are grounded in this paper and cite their sources.
GPR39 SNPs and microglial expression in MCI warrant targeted study; leaves open any biomarker or therapeutic role in VCI.
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.
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Davis et al. (2021) conducted an observational in Mild cognitive impairment (MCI) and vascular cognitive impairment (VCI). GPR39 expression and single nucleotide polymorphisms (SNPs) vs. Control subjects, young brains, and wild-type/heterozygous SNP carriers was evaluated on GPR39 expression, localization, and correlation of SNPs with white matter hyperintensity (WMH) burden. GPR39 expression was increased in aged brains, and homozygous GPR39 SNP carriers were found only in the MCI group, showing higher white matter hyperintensity volume than other genotypes.
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