Section of Neuropathology, Department of Pathology and Laboratory Medicine, Ronald Reagan UCLA Medical Center and David Geffen School of Medicine, Los Angeles, CA, USA.
Brain Research Institute, University of California, Los Angeles, CA, USA.
J Neuropathol Exp Neurol. 2022 Jun 20;81(7):565-576. doi: 10.1093/jnen/nlac040.
The elderly HIV-positive population is growing due to the widespread use of combination antiretroviral therapy (cART), but the effects of longstanding HIV infection on brain aging are unknown. A significant proportion of HIV-positive individuals develop HIV-associated neurocognitive disorder (HAND) even on cART, but the pathogenesis of HAND is unknown. Although neuroinflammation is postulated to play an important role in aging and neurodegenerative diseases such as Alzheimer disease (AD), it is unclear whether HIV accelerates aging or increases the risk for AD. We examined the brains of 9 elderly HIV-positive subjects on cART without co-infection by hepatitis C virus compared to 7 elderly HIV-negative subjects. Microglial and astrocyte activation and AD pathologic change in association with systemic comorbidities and neurocognitive assessment were evaluated. There was no difference in microglial or astrocyte activation between our HIV-positive and HIV-negative cohorts. One HIV-positive subject and 2 HIV-negative subjects demonstrated significant amyloid deposition, predominantly in the form of diffuse senile plaques, but these individuals were cognitively normal. Neurofibrillary tangles were sparse in the HIV-positive cohort. There was a high prevalence of cardiovascular comorbidities in all subjects. These findings suggest that multiple factors likely contribute to aging and cognitive impairment in elderly HIV-positive individuals on cART.
由于联合抗逆转录病毒疗法(cART)的广泛应用,老年 HIV 阳性人群正在不断增加,但长期 HIV 感染对大脑衰老的影响尚不清楚。尽管 cART 能显著降低 HIV 载量,但相当一部分 HIV 阳性个体仍会发展为 HIV 相关神经认知障碍(HAND),HAND 的发病机制尚不清楚。虽然神经炎症被认为在衰老和阿尔茨海默病(AD)等神经退行性疾病中起重要作用,但 HIV 是否会加速衰老或增加 AD 的风险尚不清楚。我们比较了 9 名接受 cART 治疗且无丙型肝炎病毒合并感染的老年 HIV 阳性患者和 7 名老年 HIV 阴性患者的大脑,评估了与全身合并症和神经认知评估相关的小胶质细胞和星形胶质细胞激活以及 AD 病理变化。我们发现 HIV 阳性和 HIV 阴性队列之间的小胶质细胞或星形胶质细胞激活没有差异。1 名 HIV 阳性患者和 2 名 HIV 阴性患者表现出明显的淀粉样蛋白沉积,主要表现为弥漫性老年斑,但这些个体认知功能正常。HIV 阳性队列中神经原纤维缠结稀少。所有受试者均存在较高的心血管合并症患病率。这些发现表明,多种因素可能导致接受 cART 治疗的老年 HIV 阳性个体衰老和认知障碍。