Abstract
BACKGROUND: HIV-associated neurocognitive disorders (HAND) persist despite the widespread implementation of combined antiretroviral therapy (ART). As people with HIV (PWH) age on ART regimens, the risk of age-related comorbidities, such as Alzheimer's disease may increase. However, questions remain as to whether HIV or ART will alter such risks. Beta amyloid (Aβ) and phosphorylated-tau (p-tau) proteins are associated with Alzheimer's disease and their levels are altered in the CSF of Alzheimer's disease cases. METHODS: To better understand how these Alzheimer's disease-related markers are affected by HIV infection and ART, postmortem CSF collected from 70 well characterized HIV+ decedents was analyzed for Aβ1-42, Aβ1-40, and p-tau levels. RESULTS: Aβ1-42 and Aβ1-40 CSF levels were higher in cases that were exposed to ART. Aβ1-42 and Aβ1-40 CSF levels were also higher in cases on protease inhibitors compared with those with no exposure to protease inhibitors. Aβ1-42 and Aβ1-40 levels in CSF were lowest in HIV+ cases with HIV-associated dementia (HAD) and levels were highest in those diagnosed with asymptomatic neurocognitive impairment (ANI) and minor neurocognitive disorder (MND). Aβ1-42 and Aβ1-40 were inversely related with p-tau levels in all cases, as previously reported. CONCLUSION: These data suggest that ART exposure is associated with increased levels of Aβ1-42 and Aβ1-40 in the CSF. Also, HAD, but not ANI/MND diagnosis is associated with decreased levels of Aβ1-42 and Aβ1-40 in CSF, potentially suggesting impaired clearance. These data suggest that HIV infection and ART may impact pathogenic mechanisms involving Aβ1-42 and Aβ1-40, but not p-tau.