title: Role of HIV in amyloid metabolism.
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.
authors.affiliation: Department of Neurology, School of Medicine, Washington University in St. Louis, Box 8111, 660 South Euclid Ave, Saint Louis, MO, 63110, USA.
authors.forename: Mario
authors.initials: M
authors.lastname: Ortega
authors.forename: Beau M
authors.initials: BM
authors.lastname: Ances
mesh_terms: D000375:Aging / Q000378:metabolism; D000544:Alzheimer Disease / Q000150:complications* / Q000378:metabolism; D016229:Amyloid beta-Peptides / Q000134:cerebrospinal fluid / Q000378:metabolism*; D015415:Biomarkers / Q000134:cerebrospinal fluid / Q000378:metabolism; D001921:Brain / Q000378:metabolism*; D003072:Cognition Disorders / Q000150:complications / Q000378:metabolism; D059907:Functional Neuroimaging; D006679:HIV Seropositivity / Q000150:complications* / Q000378:metabolism*; D006801:Humans; D008959:Models, Neurological; D010446:Peptide Fragments / Q000134:cerebrospinal fluid / Q000378:metabolism*; D049268:Positron-Emission Tomography
chemical_list: D016229:Amyloid beta-Peptides; D015415:Biomarkers; D010446:Peptide Fragments; C075222:amyloid beta-protein (1-42)