GPR39 localization in the aging human brain and correlation of expression and polymorphism with vascular cognitive impairment.
GPR39
microglia
mild cognitive impairment
polymorphism
vascular cognitive impairment
white matter hyperintensity
Journal
Alzheimer's & dementia (New York, N. Y.)
ISSN: 2352-8737
Titre abrégé: Alzheimers Dement (N Y)
Pays: United States
ID NLM: 101650118
Informations de publication
Date de publication:
2021
2021
Historique:
received:
23
12
2020
revised:
24
06
2021
accepted:
11
08
2021
entrez:
25
10
2021
pubmed:
26
10
2021
medline:
26
10
2021
Statut:
epublish
Résumé
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. We performed GPR39 immunohistochemical analysis in 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. GPR39 may play a role in aging-related VCI, and may serve as a therapeutic target and biomarker for the risk of developing VCI.
Identifiants
pubmed: 34692987
doi: 10.1002/trc2.12214
pii: TRC212214
pmc: PMC8515554
doi:
Types de publication
Journal Article
Langues
eng
Pagination
e12214Subventions
Organisme : NINDS NIH HHS
ID : R01 NS108501
Pays : United States
Informations de copyright
© 2021 The Authors. Alzheimer's & Dementia: Diagnosis, Assessment & Disease Monitoring published by Wiley Periodicals, LLC on behalf of Alzheimer's Association.
Déclaration de conflit d'intérêts
NJA 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) that 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 central nervous system 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 also received compensation from National Institutes of Health for grant reviews, and honoraria from academic universities for invited lectures. 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.
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