Department of Medicine, Jackson Memorial Hospital, University of Miami Miller School of Medicine, Miami, FL 33136, USA.
Department of Psychiatry and Behavioral Sciences, University of Miami Miller School of Medicine, Miami, FL 33136, USA.
Int J Mol Sci. 2024 Oct 17;25(20):11170. doi: 10.3390/ijms252011170.
HIV-associated neurocognitive disorder (HAND) and Alzheimer's disease (AD) are two neurocognitive disorders with overlapping clinical presentations and pathophysiology. The two have been thought to be two separate entities. However, the introduction and widespread use of antiretroviral therapy (ART) has altered the clinical manifestations of HAND, shifting from a pattern of subcortical dementia to one more akin to cortical dementia, resembling AD. Thus, the line between the two disease entities is not clear-cut. In this review, we discuss the concept of Alzheimer's disease-like dementia (ADLD) in HIV, which describes this phenomenon. While the mechanisms of HIV-associated ADLD remain to be elucidated, potential mechanisms include HIV-specific pathways, including epigenetic imprinting from initial viral infection, persistent and low viral load (which can only be detected by ultra-sensitive PCR), HIV-related inflammation, and putative pathways underlying traditional AD risk factors. Importantly, we have shown that HIV-specific microRNAs (miRs) encapsulated in extracellular vesicles (EV-miRs) play an important role in mediating the detrimental effects in the cardiovascular system. A useful preclinical model to study ADLD would be to expose AD mice to HIV-positive EVs to identify candidate EV-miRs that mediate the HIV-specific effects underlying ADLD. Characterization of the candidate EV-miRs may provide novel therapeutic armamentaria for ADLD.
HIV 相关神经认知障碍（HAND）和阿尔茨海默病（AD）是两种具有重叠临床表现和病理生理学的神经认知障碍。这两种疾病一直被认为是两种独立的实体。然而，抗逆转录病毒疗法（ART）的引入和广泛使用改变了 HAND 的临床表现，从皮质下痴呆模式转变为更类似于皮质痴呆的模式，类似于 AD。因此，这两种疾病实体之间的界限并不清晰。在这篇综述中，我们讨论了 HIV 中描述这种现象的阿尔茨海默病样痴呆（ADLD）的概念。虽然 HIV 相关性 ADLD 的机制仍有待阐明，但潜在的机制包括 HIV 特异性途径，包括初始病毒感染的表观遗传印迹、持续和低病毒载量（只能通过超灵敏 PCR 检测到）、HIV 相关炎症以及传统 AD 危险因素的潜在途径。重要的是，我们已经表明，包裹在细胞外囊泡（EV-miRs）中的 HIV 特异性 microRNAs（miRs）在介导心血管系统的有害影响中发挥重要作用。一种研究 ADLD 的有用临床前模型是使 AD 小鼠暴露于 HIV 阳性 EV 中，以鉴定介导 ADLD 下 HIV 特异性作用的候选 EV-miRs。候选 EV-miRs 的特征可能为 ADLD 提供新的治疗手段。
