Predictors of hippocampal tauopathy in people with and at risk for human immunodeficiency virus infection.
Title | Predictors of hippocampal tauopathy in people with and at risk for human immunodeficiency virus infection. |
Publication Type | Journal Article |
Year of Publication | 2023 |
Authors | Nader, S, Karlovich, E, Cortes, EP, Insausti, R, Meloni, G, Jacobs, M, Crary, JF, Morgello, S |
Journal | J Neurovirol |
Date Published | 2023 Nov 05 |
ISSN | 1538-2443 |
Abstract | Combination antiretroviral therapy (cART) has extended lifespans of people living with HIV (PWH), increasing both the risk for age-related neuropathologies and the importance of distinguishing effects of HIV and its comorbidities from neurodegenerative disorders. The accumulation of hyperphosphorylated tau (p-tau) in hippocampus is a common degenerative change, with specific patterns of hippocampal subfield vulnerability observed in different disease contexts. Currently, associations between chronic HIV, its comorbidities, and p-tau burden and distribution in the hippocampus are unexplored. We used immunohistochemistry with antibody AT8 to analyze hippocampal p-tau in brain tissues of PWH (n = 71) and HIV negative controls (n = 25), for whom comprehensive clinical data were available. Using a morphology-based neuroanatomical segmentation protocol, we annotated digital slide images to measure percentage p-tau areas in the hippocampus and its subfields. Factors predicting p-tau burden and distribution were identified in univariate analyses, and those with significance at p ≤ 0.100 were advanced to multivariable regression. The patient sample had a mean age of 61.5 years. Age predicted overall hippocampal p-tau burden. Subfield p-tau predictors were for Cornu Ammonis (CA)1, age; for CA2 and subiculum, seizure history; for CA3, seizure history and head trauma; and for CA4/dentate, history of hepatitis C virus (HCV) infection. In this autopsy sample, hippocampal p-tau burden and distribution were not predicted by HIV, viral load, or immunologic status, with viral effects limited to associations between HCV and CA4/dentate vulnerability. Hippocampal p-tau pathologies in cART-era PWH appear to reflect age and comorbidities, but not direct effects of HIV infection. |
DOI | 10.1007/s13365-023-01181-9 |
Alternate Journal | J Neurovirol |
PubMed ID | 37926797 |
PubMed Central ID | 7899277 |
Grant List | U24MH100931 / MH / NIMH NIH HHS / United States RF01AG060961 / AG / NIA NIH HHS / United States RO1AG054008 / AG / NIA NIH HHS / United States RO1AG062348 / AG / NIA NIH HHS / United States P30AG066514 / AG / NIA NIH HHS / United States RF1NS095252 / NS / NINDS NIH HHS / United States RO1NS086736 / NS / NINDS NIH HHS / United States U54NS115266 / NS / NINDS NIH HHS / United States |