RT Journal Article
SR Electronic
T1 GPR39 Localization in Aging Human Brain and Correlation of Expression and Polymorphism with Vascular Cognitive Impairment
JF bioRxiv
FD Cold Spring Harbor Laboratory
SP 2021.07.15.452525
DO 10.1101/2021.07.15.452525
A1 Catherine M Davis
A1 Thierno M Bah
A1 Wenri H Zhang
A1 Jonathan W Nelson
A1 Kirsti Golgotiu
A1 Xiao Nie
A1 Farah N Alkayed
A1 Jennifer M Young
A1 Randy L Woltjer
A1 Lisa C Silbert
A1 Marjorie R Grafe
A1 Nabil J Alkayed
YR 2021
UL http://biorxiv.org/content/early/2021/07/15/2021.07.15.452525.abstract
AB 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 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.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 WT 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.Competing Interest StatementNJA is co-inventor of GPR39-targeting compounds that have been licensed to a company with a commercial interest in the results; in the past 36 months NJA co-founded then sold shares in a company (Vasocardea) which was formed to develop GPR39-targeting drugs and diagnostic probes. He is also founder of another company (NeuvaRx) formed to develop GPR39-targeting drugs and diagnostic probes for CNS disorders. This potential conflict of interest has been reviewed and managed by OHSU. NJA has received royalties for a co-invention ([18F]FNDP for PET Imaging of Soluble Epoxide Hydrolase) licensed to Precision Molecular. NJA has one patent issued (WO2017192854A1: Radiofluorinated FNDP for PET imaging of soluble epoxide hydrolase (sEH), and two other provisional patents are pending (Use of GPR39 probes and ligands for the diagnosis and treatment of cardiovascular disease and biomarkers for detection of coronary artery disease and its management). KG has received consultant fees from OHSU for coding tools. Other authors have declared that no conflict of interest exists. This work was supported by NIH grant to NJA 1RF1AG058273-01.