Abstract
The longevity of people with HIV/AIDS has been prolonged with the use of antiretroviral therapy (ART). The age-related complications, especially cognitive deficits, rise as HIV patients live longer. Deposition of beta-amyloid (Aβ), a hallmark of Alzheimer’s disease (AD), has been observed in subjects with HIV-associated neurocognitive disorders (HAND). Various mechanisms such as neuroinflammation induced by HIV proteins (e.g., Tat, gp120, Nef), excitotoxicity, oxidative stress, and the use of ART contribute to the deposition of Aβ, leading to dementia. However, progressive dementia in older subjects with HIV might be due to HAND, AD, or both. Recently, extracellular vesicles (EVs)/exosomes, have gained recognition for their importance in understanding the pathology of both HAND and AD. EVs can serve as a possible link between HIV and AD, due to their ability to package and transport the toxic proteins implicated in both AD and HIV (Aβ/tau and gp120/tat, respectively). Given that Aß is also elevated in neuron-derived exosomes isolated from the plasma of HIV patients, it is reasonable to suggest that neuron-to-neuron exosomal transport of Aβ and tau also contributes to AD-like pathology in HIV-infected subjects. Therefore, exploring exosomal contents is likely to help distinguish HAND from AD. However, future prospective clinical studies need to be conducted to compare the exosomal contents in the plasma of HIV subjects with and without HAND as well as those with and without AD. This would help to find new markers and develop new treatment strategies to treat AD in HIV-positive subjects. This review presents comprehensive literatures on the mechanisms contributing to Aβ deposition in HIV-infected cells, the role of EVs in the propagation of Aβ in AD, the possible role of EVs in HIV-induced AD-like pathology, and finally, possible therapeutic targets or molecules to treat HIV subjects with AD.
Highlights
According to the latest data from the United Nations Programme on HIV/AIDS (UNAIDS), there were approximately 36.9 million people living with HIV/AIDS globally in 2017 [1]
Various mechanisms involved in the HIV infection of macrophages, microglia, and astrocytes may play a robust role in neuronal injury and in the interruption of normal neurological mechanisms, contributing to HIV-associated dementia or Alzheimer’s disease (AD)
Sinha et al have demonstrated that extracellular vesicles (EVs)/exosomes may play a major role in neuron-to-neuron transportation of the toxic proteins amyloid beta (Aβ) and tau, contributing to the pathogenesis of AD [23]
Summary
According to the latest data from the United Nations Programme on HIV/AIDS (UNAIDS), there were approximately 36.9 million people living with HIV/AIDS globally in 2017 [1]. 47% of people living with HIV or AIDS in the United States were aged 55 or older [3] As they live longer, the prevalence of age-related comorbidities, neurocognitive disorders, cardiovascular diseases, and cancer increase in the HIV-infected population. Alzheimer’s disease (AD) is the most common age-related neurodegenerative disease It is characterized by progressive memory loss and declining cognitive function and is the fifth leading cause of death in people over the age of 65 [8]. EVs (mainly exosomes) have gained recognition for their importance in understanding the pathology of HIV-induced neurodegenerative disorders, as they have been reported to package the HIV viral proteins Tat, gp-120, and Nef, which can induce neurotoxicity [15,16,17,18,19]. We briefly discuss the mechanisms contributing to amyloid beta deposition (a hallmark of AD) in HIV infection, the role of EVs in propagating AD, and a proposed role for EVs in developing AD in HIV subjects
Sign-in/Register to view highlights & summary Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
