Beta amyloid levels in cerebrospinal fluid of HIV-infected people vary by exposure to antiretroviral therapy

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 Aβ 1–42, Aβ 1–40, and p-tau levels. Results: Aβ 1–42 and Aβ 1–40 CSF levels were higher in cases that were exposed to ART. Aβ 1–42 and Aβ 1–40 CSF levels were also higher in cases on protease inhibitors compared with those with no exposure to protease inhibitors. Aβ 1–42 and Aβ 1–40 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). Aβ 1–42 and Aβ 1–40 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 Aβ 1–42 and Aβ 1–40 in the CSF. Also, HAD, but not ANI/MND diagnosis is associated with decreased levels of Aβ 1–42 and Aβ 1–40 in CSF, potentially suggesting impaired clearance. These data suggest that HIV infection and ART may impact pathogenic mechanisms involving Aβ 1–42 and Aβ 1–40, but not p-tau.