@article{abf9e7b2c6c940b5a05c4a215b5f5d09,
title = "GPR39 localization in the aging human brain and correlation of expression and polymorphism with vascular cognitive impairment",
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.",
author = "Davis, {Catherine M.} and Bah, {Thierno M.} and Zhang, {Wenri H.} and Nelson, {Jonathan W.} and Kirsti Golgotiu and Xiao Nie and Alkayed, {Farah N.} and Young, {Jennifer M.} and Woltjer, {Randy L.} and Silbert, {Lisa C.} and Grafe, {Marjorie R.} and Alkayed, {Nabil J.}",
note = "Funding Information: We would like to acknowledge expert technical assistance by staff in the OHSU Advanced Light Microscopy Core, supported by grant P30NS061800 and OHSU Biostatistics & Design Program (partially supported by the Oregon Clinical and Translational Research Institute [UL1TR002369]) for data analysis expertise. DNA quality assessment and qPCR assays were performed in the OHSU Gene Profiling Shared Resource, which receives support from the OHSU Knight Cancer Institute NCI Cancer Center Support Grant P30CA069533. We thank the Oregon Alzheimer's Disease Research Center (NIA P30AG066518, P30AG008017) and the Department of Veterans Affairs. In the past 36 months the following authors have received support outside this project: CMD, Oregon Partnership for Alzheimer's Research; JWN, NIH 1K01DK121737; LCS, NIH/NIA R01 AG056712; NJA, NINDS R01 NS108501. This work was supported by NIH grant to NJA 1RF1AG058273‐01. Funding Information: We would like to acknowledge expert technical assistance by staff in the OHSU Advanced Light Microscopy Core, supported by grant P30NS061800 and OHSU Biostatistics & Design Program (partially supported by the Oregon Clinical and Translational Research Institute [UL1TR002369]) for data analysis expertise. DNA quality assessment and qPCR assays were performed in the OHSU Gene Profiling Shared Resource, which receives support from the OHSU Knight Cancer Institute NCI Cancer Center Support Grant P30CA069533. We thank the Oregon Alzheimer's Disease Research Center (NIA P30AG066518, P30AG008017) and the Department of Veterans Affairs. In the past 36 months the following authors have received support outside this project: CMD, Oregon Partnership for Alzheimer's Research; JWN, NIH 1K01DK121737; LCS, NIH/NIA R01 AG056712; NJA, NINDS R01 NS108501. This work was supported by NIH grant to NJA 1RF1AG058273-01. Publisher Copyright: {\textcopyright} 2021 The Authors. Alzheimer's & Dementia: Diagnosis, Assessment & Disease Monitoring published by Wiley Periodicals, LLC on behalf of Alzheimer's Association.",
year = "2021",
doi = "10.1002/trc2.12214",
language = "English (US)",
volume = "7",
journal = "Alzheimer's and Dementia: Translational Research and Clinical Interventions",
issn = "2352-8737",
publisher = "Elsevier Inc.",
number = "1",
}