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
Department of Anesthesiology & Perioperative Medicine Oregon Health & Science University Portland Oregon USA.
Division of Nephrology and Hypertension, Department of Medicine Oregon Health & Science University Portland Oregon USA.
Alzheimers Dement (N Y). 2021 Oct 14;7(1):e12214. doi: 10.1002/trc2.12214. eCollection 2021.
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 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 magnetic resonance imaging.
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.
血管性认知障碍（VCI）的发病机制尚未完全明确。GPR39是一种孤儿G蛋白偶联受体，与神经疾病有关，但其在VCI中的作用尚不清楚。
我们对轻度认知障碍（MCI）患者和对照受试者的脑样本进行了GPR39免疫组织化学分析。分析了GPR39单核苷酸多态性（SNP）的DNA，并将其与磁共振成像上的白质高信号（WMH）负荷相关联。
GPR39在老年人类背外侧前额叶皮质中表达，定位于小胶质细胞和类似于周细胞的毛细血管周围细胞。与年轻大脑相比，老年大脑中GPR39与毛细血管的共定位以及表达GPR39的小胶质细胞密度增加。两组之间SNP分布相同；然而，纯合SNP携带者仅存在于MCI组中，并且其WMH体积高于野生型或杂合SNP携带者。
GPR39可能在与衰老相关的VCI中起作用，并可能作为VCI发生风险的治疗靶点和生物标志物。
