Boustani Ali, Ford Mary K, Kulbe Jacqueline R, Laird Anna E, Shu Leeann, Spencer Matthew, Avalos Bryant, Walter Kyle C, Ellis Ronald J, Fields Jerel Adam
Department of Psychiatry, University of California San Diego, San Diego, CA 92093, USA.
Department of Neurosciences, University of California San Diego, San Diego, CA 92093, USA.
Brain Sci. 2025 Jan 7;15(1):49. doi: 10.3390/brainsci15010049.
: HIV-associated neurocognitive impairment (NCI) remains a prevalent issue among people with HIV (PWH) despite advancements in antiretroviral therapy (ART). The pathogenesis of HIV-associated NCI is linked to chronic neuroinflammation caused by HIV, even in those with successful viral suppression. Growth Differentiation Factor 15 (GDF15), a protein involved in inflammatory and metabolic stress responses, has emerged as a key player and potential biomarker for various neurological conditions. This study investigates the relationship between GDF15 expression and HIV-associated NCI. : PWH from the California NeuroAIDS Tissue Network (CNTN) underwent comprehensive neuropsychological exams within 12 months before death and were categorized based on cognitive performance. We examined GDF15 levels in their CSF (Cerebrospinal Fluid) and brain tissues using immunoblotting, immunohistochemistry, double immunolabeling, and ELISA. : The cohort was of a similar age across HIV-associated NCI statuses (mean = 40.5), with a predominance of males (77%). The mean plasma viral load was 3.56 log copies/mL for Neurocognitively Unimpaired (NUI) PWH and 5.38 log10 copies/mL for people with HIV-associated NCI. GDF15 protein levels were significantly elevated in the frontal cortices of PWH with NCI compared to NUI PWH. : The findings indicate that GDF15 may play a role in the pathogenesis of HIV-associated NCI, possibly through neuroinflammatory mechanisms. The strong association between GDF15 levels and cognitive impairment severity suggests its potential as a biomarker for the early detection and monitoring of NCI in PWH.
尽管抗逆转录病毒疗法（ART）取得了进展，但人类免疫缺陷病毒（HIV）相关神经认知障碍（NCI）在HIV感染者（PWH）中仍然是一个普遍存在的问题。HIV相关NCI的发病机制与HIV引起的慢性神经炎症有关，即使在病毒抑制成功的患者中也是如此。生长分化因子15（GDF15）是一种参与炎症和代谢应激反应的蛋白质，已成为各种神经系统疾病的关键因素和潜在生物标志物。本研究调查了GDF15表达与HIV相关NCI之间的关系。来自加利福尼亚神经艾滋病组织网络（CNTN）的PWH在死亡前12个月内接受了全面的神经心理学检查，并根据认知表现进行了分类。我们使用免疫印迹、免疫组织化学、双重免疫标记和酶联免疫吸附测定（ELISA）检测了他们脑脊液（CSF）和脑组织中的GDF15水平。该队列在HIV相关NCI状态下年龄相似（平均 = 40.5岁），男性占主导（77%）。神经认知未受损（NUI）的PWH平均血浆病毒载量为3.56 log拷贝/mL，而HIV相关NCI患者为5.38 log10拷贝/mL。与NUI的PWH相比，NCI的PWH额叶皮质中的GDF15蛋白水平显著升高。研究结果表明，GDF15可能在HIV相关NCI的发病机制中起作用，可能是通过神经炎症机制。GDF15水平与认知障碍严重程度之间的密切关联表明其有潜力作为PWH中NCI早期检测和监测的生物标志物。
