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Extracellular Vesicles: A Possible Link between HIV and Alzheimer's Disease-Like Pathology in HIV Subjects?
Cells. 2019 08 24; 8(9)C

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 Aβ 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.

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Authors+Show Affiliations

Kodidela S
Department of Pharmaceutical Sciences, University of Tennessee Health Science Center, 881 Madison Ave, Memphis, TN 38163, USA. skodidel@uthsc.edu.
Gerth K
Department of Pharmaceutical Sciences, University of Tennessee Health Science Center, 881 Madison Ave, Memphis, TN 38163, USA.
Haque S
Department of Pharmaceutical Sciences, University of Tennessee Health Science Center, 881 Madison Ave, Memphis, TN 38163, USA.
Gong Y
Department of Pharmaceutical Sciences, University of Tennessee Health Science Center, 881 Madison Ave, Memphis, TN 38163, USA.
Ismael S
Department of Anatomy and Neurobiology, The University of Tennessee Health Science Center, 855 Monroe Avenue #515, Memphis, TN 38163, USA.
Singh A
Department of Pediatric Pulmonology, Le Bonheur Children Hospital, 50 N. Dunlap st, Memphis, TN 38103, USA.
Tauheed I
Department of Anatomy and Neurobiology, The University of Tennessee Health Science Center, 855 Monroe Avenue #515, Memphis, TN 38163, USA.
Kumar S
Department of Pharmaceutical Sciences, University of Tennessee Health Science Center, 881 Madison Ave, Memphis, TN 38163, USA. ksantosh@uthsc.edu.

MeSH

Age FactorsAlzheimer DiseaseAmyloid beta-PeptidesAnti-Retroviral AgentsExtracellular VesiclesHIV InfectionsHumans

Pub Type(s)

Journal Article
Research Support, N.I.H., Extramural
Review

Language

eng

PubMed ID

31450610

Citation

Kodidela, Sunitha, et al. "Extracellular Vesicles: a Possible Link Between HIV and Alzheimer's Disease-Like Pathology in HIV Subjects?" Cells, vol. 8, no. 9, 2019.
Kodidela S, Gerth K, Haque S, et al. Extracellular Vesicles: A Possible Link between HIV and Alzheimer's Disease-Like Pathology in HIV Subjects? Cells. 2019;8(9).
Kodidela, S., Gerth, K., Haque, S., Gong, Y., Ismael, S., Singh, A., Tauheed, I., & Kumar, S. (2019). Extracellular Vesicles: A Possible Link between HIV and Alzheimer's Disease-Like Pathology in HIV Subjects? Cells, 8(9). https://doi.org/10.3390/cells8090968
Kodidela S, et al. Extracellular Vesicles: a Possible Link Between HIV and Alzheimer's Disease-Like Pathology in HIV Subjects. Cells. 2019 08 24;8(9) PubMed PMID: 31450610.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Extracellular Vesicles: A Possible Link between HIV and Alzheimer's Disease-Like Pathology in HIV Subjects? AU - Kodidela,Sunitha, AU - Gerth,Kelli, AU - Haque,Sanjana, AU - Gong,Yuqing, AU - Ismael,Saifudeen, AU - Singh,Ajay, AU - Tauheed,Ishrat, AU - Kumar,Santosh, Y1 - 2019/08/24/ PY - 2019/07/16/received PY - 2019/08/20/revised PY - 2019/08/21/accepted PY - 2019/8/28/entrez PY - 2019/8/28/pubmed PY - 2020/5/19/medline KW - Alzheimer’s disease KW - HAND KW - HIV KW - HIV-TAT KW - beta-amyloid KW - exosomes KW - extracellular vesicles (EVs) KW - neurodegeneration JF - Cells JO - Cells VL - 8 IS - 9 N2 - 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 Aβ 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. SN - 2073-4409 UR - https://www.unboundmedicine.com/medline/citation/31450610/Extracellular_Vesicles:_A_Possible_Link_between_HIV_and_Alzheimer's_Disease_Like_Pathology_in_HIV_Subjects DB - PRIME DP - Unbound Medicine ER -