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Does HIV infection contribute to increased beta-amyloid synthesis and plaque formation leading to neurodegeneration and Alzheimer’s disease?

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Abstract

HIV infection in the combination antiretroviral therapy (cART) era has become a chronic disease with a life expectancy almost identical to those free from this infection. Concomitantly, chronic diseases such as neurodegenerative diseases have emerged as serious clinical problems. HIV-induced cognitive changes, although clinically very diverse are collectively called HIV-associated neurocognitive disorder (HAND). HAND, which until the introduction of cART manifested clinically as a subcortical disorder, is now considered primarily cognitive disorder, which makes it similar to diseases like Alzheimer’s (AD) and Parkinson’s disease (PD). The pathogenesis involves either the direct effects of the virus or the effect of viral proteins such as Tat, Ggp120, and Nef. These proteins are either capable of destroying neurons directly by inducing neurotoxic mediators or by initiating neuroinflammation by microglia and astrocytes. Recently, it has become recognized that HIV infection is associated with increased production of the beta-amyloid peptide (Aβ) which is a characteristic of AD. Moreover, amyloid plaques have also been demonstrated in the brains of patients suffering from HAND. Thus, the question arises whether this production of Aβ indicates that HAND may lead to AD or it is a form of AD or this increase in Aβ production is only a bystander effect. It has also been discovered that APP in HIV and its metabolic product Aβ in AD manifest antiviral innate immune peptide characteristics. This review attempts to bring together studies linking amyloid precursor protein (APP) and Aβ production in HIV infection and their possible impact on the course of HAND and AD. These data indicate that human defense mechanisms in HAND and AD are trying to contain microorganisms by antimicrobial peptides, however by employing different means. Future studies will, no doubt, uncover the relationship between HAND and AD and, hopefully, reveal novel treatment possibilities.

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Acknowledgments

This work was supported by grants from the Canadian Institutes of Health Research (CIHR) (No. 106634), the Société des médecins de l’Université de Sherbrooke and the Research Center on Aging of the CIUSSS-CHUS, Sherbrooke and the FRQS Audace grant to TF and EF; by the Polish Ministry of Science and Higher Education statutory grant 02-0058/07/262 to JMW; by Agency for Science Technology and Research (A*STAR) to AL and GH was supported by a grant from the Université de Franche-Comté.

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Authors and Affiliations

  1. Research Center on Aging, Geriatric Division, Department of Medicine, Faculty of Medicine and Health Sciences, University of Sherbrooke, 3001, 12th Avenue North, Sherbrooke, Quebec, J1H 5N4, Canada

    Tamas Fulop & Abdelouahed Khalil

  2. Department of Pathophysiology, Medical University of Gdansk, Gdansk, Poland

    Jacek M. Witkowski

  3. Singapore Immunology Network (SIgN), Agency for Science Technology and Research (A*STAR), Immunos Building, Biopolis, Singapore, Singapore

    Anis Larbi

  4. Department of Biology, Faculty of Science, University Tunis El Manar, Tunis, Tunisia

    Anis Larbi

  5. Department Pathogens & Inflammation-EPILAB, UPRES EA4266, Université of Franche-Comté (UFC), University of Bourgogne France-Comté (UBFC), F-25030, Besançon, France

    Georges Herbein

  6. Department of Virology, CHRU Besancon, F-25030, Besancon, France

    Georges Herbein

  7. Department of Microbiology and Infectious Diseases, Faculty of Medicine and Health Sciences, University of Sherbrooke, Sherbrooke, Quebec, Canada

    Eric H. Frost

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Fulop, T., Witkowski, J.M., Larbi, A. et al. Does HIV infection contribute to increased beta-amyloid synthesis and plaque formation leading to neurodegeneration and Alzheimer’s disease?. J. Neurovirol. 25, 634–647 (2019). https://doi.org/10.1007/s13365-019-00732-3

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