Role of HIV in Amyloid Metabolism

J Neuroimmune Pharmacol. 2014 Sep;9(4):483-91. doi: 10.1007/s11481-014-9546-0. Epub 2014 May 10.

Abstract

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 [(11)C] 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 [(11)C] 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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Aging / metabolism
  • Alzheimer Disease / complications*
  • Alzheimer Disease / metabolism
  • Amyloid beta-Peptides / cerebrospinal fluid
  • Amyloid beta-Peptides / metabolism*
  • Biomarkers / cerebrospinal fluid
  • Biomarkers / metabolism
  • Brain / metabolism*
  • Cognition Disorders / complications
  • Cognition Disorders / metabolism
  • Functional Neuroimaging
  • HIV Seropositivity / complications*
  • HIV Seropositivity / metabolism*
  • Humans
  • Models, Neurological
  • Peptide Fragments / cerebrospinal fluid
  • Peptide Fragments / metabolism*
  • Positron-Emission Tomography

Substances

  • Amyloid beta-Peptides
  • Biomarkers
  • Peptide Fragments
  • amyloid beta-protein (1-42)