Alzheimer’s-Like Pathology at the Crossroads of HIV-Associated Neurological Disorders
Despite the widespread success of combined antiretroviral therapy (cART) in suppressing viremia, the prevalence of human immunodeficiency virus (HIV)-associated neurological disorders (HAND) and associated comorbidities such as Alzheimer’s disease (AD)-like symptomatology is higher among people livi...
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MDPI AG
2021-08-01
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| Series: | Vaccines |
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| Online Access: | https://www.mdpi.com/2076-393X/9/8/930 |
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| author | Divya T. Chemparthy Muthukumar Kannan Lila Gordon Shilpa Buch Susmita Sil |
| author_facet | Divya T. Chemparthy Muthukumar Kannan Lila Gordon Shilpa Buch Susmita Sil |
| author_sort | Divya T. Chemparthy |
| collection | DOAJ |
| description | Despite the widespread success of combined antiretroviral therapy (cART) in suppressing viremia, the prevalence of human immunodeficiency virus (HIV)-associated neurological disorders (HAND) and associated comorbidities such as Alzheimer’s disease (AD)-like symptomatology is higher among people living with HIV. The pathophysiology of observed deficits in HAND is well understood. However, it has been suggested that it is exacerbated by aging. Epidemiological studies have suggested comparable concentrations of the toxic amyloid protein, amyloid-β42 (Aβ42), in the cerebrospinal fluid (CSF) of HAND patients and in the brains of patients with dementia of the Alzheimer’s type. Apart from abnormal amyloid-β (Aβ) metabolism in AD, a better understanding of the role of similar pathophysiologic processes in HAND could be of substantial value. The pathogenesis of HAND involves either the direct effects of the virus or the effect of viral proteins, such as Tat, Gp120, or Nef, as well as the effects of antiretrovirals on amyloid metabolism and tauopathy, leading, in turn, to synaptodendritic alterations and neuroinflammatory milieu in the brain. Additionally, there is a lack of knowledge regarding the causative or bystander role of Alzheimer’s-like pathology in HAND, which is a barrier to the development of therapeutics for HAND. This review attempts to highlight the cause–effect relationship of Alzheimer’s-like pathology with HAND, attempting to dissect the role of HIV-1, HIV viral proteins, and antiretrovirals in patient samples, animal models, and cell culture model systems. Biomarkers associated with Alzheimer’s-like pathology can serve as a tool to assess the neuronal injury in the brain and the associated cognitive deficits. Understanding the factors contributing to the AD-like pathology associated with HAND could set the stage for the future development of therapeutics aimed at abrogating the disease process. |
| first_indexed | 2024-03-10T08:18:48Z |
| format | Article |
| id | doaj.art-a0e284f2472c4222a3db7a7b2c5fc5b4 |
| institution | Directory Open Access Journal |
| issn | 2076-393X |
| language | English |
| last_indexed | 2024-03-10T08:18:48Z |
| publishDate | 2021-08-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Vaccines |
| spelling | doaj.art-a0e284f2472c4222a3db7a7b2c5fc5b42023-11-22T10:08:11ZengMDPI AGVaccines2076-393X2021-08-019893010.3390/vaccines9080930Alzheimer’s-Like Pathology at the Crossroads of HIV-Associated Neurological DisordersDivya T. Chemparthy0Muthukumar Kannan1Lila Gordon2Shilpa Buch3Susmita Sil4University of Nebraska Medical Center, Department of Pharmacology and Experimental Neuroscience, Omaha, NE 68198-5880, USAUniversity of Nebraska Medical Center, Department of Pharmacology and Experimental Neuroscience, Omaha, NE 68198-5880, USAUniversity of Nebraska Medical Center, Department of Pharmacology and Experimental Neuroscience, Omaha, NE 68198-5880, USAUniversity of Nebraska Medical Center, Department of Pharmacology and Experimental Neuroscience, Omaha, NE 68198-5880, USAUniversity of Nebraska Medical Center, Department of Pharmacology and Experimental Neuroscience, Omaha, NE 68198-5880, USADespite the widespread success of combined antiretroviral therapy (cART) in suppressing viremia, the prevalence of human immunodeficiency virus (HIV)-associated neurological disorders (HAND) and associated comorbidities such as Alzheimer’s disease (AD)-like symptomatology is higher among people living with HIV. The pathophysiology of observed deficits in HAND is well understood. However, it has been suggested that it is exacerbated by aging. Epidemiological studies have suggested comparable concentrations of the toxic amyloid protein, amyloid-β42 (Aβ42), in the cerebrospinal fluid (CSF) of HAND patients and in the brains of patients with dementia of the Alzheimer’s type. Apart from abnormal amyloid-β (Aβ) metabolism in AD, a better understanding of the role of similar pathophysiologic processes in HAND could be of substantial value. The pathogenesis of HAND involves either the direct effects of the virus or the effect of viral proteins, such as Tat, Gp120, or Nef, as well as the effects of antiretrovirals on amyloid metabolism and tauopathy, leading, in turn, to synaptodendritic alterations and neuroinflammatory milieu in the brain. Additionally, there is a lack of knowledge regarding the causative or bystander role of Alzheimer’s-like pathology in HAND, which is a barrier to the development of therapeutics for HAND. This review attempts to highlight the cause–effect relationship of Alzheimer’s-like pathology with HAND, attempting to dissect the role of HIV-1, HIV viral proteins, and antiretrovirals in patient samples, animal models, and cell culture model systems. Biomarkers associated with Alzheimer’s-like pathology can serve as a tool to assess the neuronal injury in the brain and the associated cognitive deficits. Understanding the factors contributing to the AD-like pathology associated with HAND could set the stage for the future development of therapeutics aimed at abrogating the disease process.https://www.mdpi.com/2076-393X/9/8/930HANDADtauopathyAβ42synaptodendritic alterations |
| spellingShingle | Divya T. Chemparthy Muthukumar Kannan Lila Gordon Shilpa Buch Susmita Sil Alzheimer’s-Like Pathology at the Crossroads of HIV-Associated Neurological Disorders Vaccines HAND AD tauopathy Aβ42 synaptodendritic alterations |
| title | Alzheimer’s-Like Pathology at the Crossroads of HIV-Associated Neurological Disorders |
| title_full | Alzheimer’s-Like Pathology at the Crossroads of HIV-Associated Neurological Disorders |
| title_fullStr | Alzheimer’s-Like Pathology at the Crossroads of HIV-Associated Neurological Disorders |
| title_full_unstemmed | Alzheimer’s-Like Pathology at the Crossroads of HIV-Associated Neurological Disorders |
| title_short | Alzheimer’s-Like Pathology at the Crossroads of HIV-Associated Neurological Disorders |
| title_sort | alzheimer s like pathology at the crossroads of hiv associated neurological disorders |
| topic | HAND AD tauopathy Aβ42 synaptodendritic alterations |
| url | https://www.mdpi.com/2076-393X/9/8/930 |
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