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The Comorbidity of HIV-Associated Neurocognitive Disorders and Alzheimer’s Disease: A Foreseeable Medical Challenge in Post-HAART Era

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Abstract

Although the introduction of highly active antiretroviral therapy (HAART) has led to a strong reduction of HIV-associated dementia (HAD) incidence, the prevalence of minor HIV-1-associated neurocognitive disorder (HAND) is rising among AIDS patients. HAART medication has shifted neuropathology from a subacute encephalitic condition to a subtle neurodegenerative process involving synaptic and dendritic degeneration, particularly of hippocampal neurons that are spared prior to HAART medication. Considerable neuroinflammation coupled with mononuclear phagocyte activation is present in HAART-medicated brains, particularly in the hippocampus. Accumulating evidence suggests that the resultant elevated secretion of pro-inflammatory cytokines such as interferon-γ, tumor necrosis factor-α, and interleukin-1β can increase amyloid-β peptide (Aβ) generation and reduce Aβ clearance. Recent advancements in Alzheimer’s disease (AD) research identified Aβ biogenesis and clearance venues that are potentially influenced by HIV viral infection, providing new insights into beta-amyloidosis segregation in HIV patients. Our study suggests enhanced beta-amyloidosis in ART-treated HAD and HIV-associated encephalitis brains and suppression of Aβ clearance by viral infection of human primary macrophages. A growing awareness of potential convergent mechanisms leading to neurodegeneration shared by HIV and Aβ points to a significant chance of comorbidity of AD and HAND in senile HIV patients, which calls for a need of basic studies.

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Acknowledgment

We thank National NeuroAIDS Tissue Banks (University of California, Los Angeles; University of California, San Diego; and University of Texas Galveston) for brain specimens; Departmental Tissue and Cell Core Facility for elutriated human monocytes; Drs. Howard Gendelman, Ben Gelman, Yuri Persidsky, Tomomi Kiyota, and Huanyu Dou for consultation in AD and HAND pathogenesis; Ms. Robin Taylor for developing schemes; and Russell Swan and Meg Marquardt for editing the manuscripts. This work was funded by NIH grant R01 MH072539, P01 NS043985, NCRR P20RR15635, and Vada Kinman Oldfield Research Award (T.I).

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  1. Department of Pharmacology and Experimental Neuroscience, Center for Neurovirology and Neurodegenerative Disorders, University of Nebraska Medical Center, Omaha, NE, 68198-5880, USA

    Jiqing Xu & Tsuneya Ikezu

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Xu, J., Ikezu, T. The Comorbidity of HIV-Associated Neurocognitive Disorders and Alzheimer’s Disease: A Foreseeable Medical Challenge in Post-HAART Era. J Neuroimmune Pharmacol 4, 200–212 (2009). https://doi.org/10.1007/s11481-008-9136-0

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