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HIV and Alzheimer’s disease: complex interactions of HIV-Tat with amyloid β peptide and Tau protein

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Abstract

In patients infected with the human immunodeficiency virus (HIV), the HIV-Tat protein may be continually produced despite adequate antiretroviral therapy. As the HIV-infected population is aging, it is becoming increasingly important to understand how HIV-Tat may interact with proteins such as amyloid β and Tau which accumulate in the aging brain and eventually result in Alzheimer’s disease. In this review, we examine the in vivo data from HIV-infected patients and animal models and the in vitro experiments that show how protein complexes between HIV-Tat and amyloid β occur through novel protein-protein interactions and how HIV-Tat may influence the pathways for amyloid β production, degradation, phagocytosis, and transport. HIV-Tat may also induce Tau phosphorylation through a cascade of cellular processes that lead to the formation of neurofibrillary tangles, another hallmark of Alzheimer’s disease. We also identify gaps in knowledge and future directions for research. Available evidence suggests that HIV-Tat may accelerate Alzheimer-like pathology in patients with HIV infection which cannot be impacted by current antiretroviral therapy.

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  1. Section of Infections of the Nervous System, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bldg 10; Room 7C-103, 10 Center Drive, Bethesda, MD, 20892, USA

    Alina Hategan & Avindra Nath

  2. Division of Neuroscience, National Institute of Aging, National Institutes of Health, 7201 Wisconsin Ave, Bethesda, MD, 20892, USA

    Eliezer Masliah

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  1. Alina Hategan
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Hategan, A., Masliah, E. & Nath, A. HIV and Alzheimer’s disease: complex interactions of HIV-Tat with amyloid β peptide and Tau protein. J. Neurovirol. 25, 648–660 (2019). https://doi.org/10.1007/s13365-019-00736-z

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