Role of HIV in Amyloid Metabolism
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HIV infection has changed from an acute devastating disease to a more chronic illness due to combination anti-retroviral treatment (cART). In the cART era, the life expectancy of HIV-infected (HIV+) individuals has increased. More HIV + individuals are aging with current projections suggesting that 50 % of HIV + individuals will be over 50 years old by 2015. With advancing age, HIV + individuals may be at increased risk of developing other potential neurodegenerative disorders [especially Alzheimer’s disease (AD)]. Pathology studies have shown that HIV increases intra and possibly extracellular amyloid beta (Aβ42), a hallmark of AD. We review the synthesis and clearance of Aβ42; the effects of HIV on the amyloid pathway; and contrast the impact of AD and HIV on Aβ42 metabolism. Biomarker studies (cerebrospinal fluid AB and amyloid imaging) in HIV + participants have shown mixed results. CSF Aβ42 has been shown to be either normal or diminished in with HIV associated neurocognitive disorders (HAND). Amyloid imaging using [11C] PiB has also not demonstrated increased extracellular amyloid fibrillar deposits in HAND. We further demonstrate that Aβ42 deposition is not increased in older HIV + participants using [11C] PiB amyloid imaging. Together, these results suggest that HIV and aging each independently affect Aβ42 deposition with no significant interaction present. Older HIV + individuals are probably not at increased risk for developing AD. However, future longitudinal studies of older HIV + individuals using multiple modalities (including the combination of CSF markers and amyloid imaging) are necessary for investigating the effects of HIV on Aβ42 metabolism.
KeywordsHIV CNS Amyloid Cerebrospinal fluid (CSF) Amyloid imaging Combination anti-retroviral therapy (cART) HIV associated neurocognitive disorders (HAND)
This work was supported by National Institutes of Health (NIH) grants R01NR014449, R01NR012657, R01NR012907, R21MH099979, and the Alzheimer’s Association (BMA).
Conflict of interest
The authors have no conflicts of interest related to this work to report.
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