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Open Access 01-12-2022 | Human Immunodeficiency Virus | Research

Frontal lobe microglia, neurodegenerative protein accumulation, and cognitive function in people with HIV

Authors: Jacinta Murray, Gregory Meloni, Etty P. Cortes, Ariadna KimSilva, Michelle Jacobs, Alyssa Ramkissoon, John F. Crary, Susan Morgello

Published in: Acta Neuropathologica Communications | Issue 1/2022

Abstract

Microglia are implicated in Alzheimer’s Disease (AD) pathogenesis. In a middle-aged cohort enriched for neuroinflammation, we asked whether microgliosis was related to neocortical amyloid beta (A\(\upbeta\)) deposition and neuronal phosphorylated tau (p-tau), and whether microgliosis predicted cognition. Frontal lobe tissue from 191 individuals autopsied with detectable (HIV-D) and undetectable (HIV-U) HIV infection, and 63 age-matched controls were examined. Immunohistochemistry (IHC) was used to evaluate A\(\upbeta\) plaques and neuronal p-tau, and quantitate microgliosis with markers Iba1, CD163, and CD68 in large regions of cortex. Glia in the A\(\upbeta\) plaque microenvironment were quantitated by immunofluorescence (IF). The relationship of microgliosis to cognition was evaluated. No relationship between A\(\upbeta\) or p-tau accumulation and overall severity of microgliosis was discerned. Individuals with uncontrolled HIV had the greatest microgliosis, but fewer A\(\upbeta\) plaques; they also had higher prevalence of APOE \(\upvarepsilon\)4 alleles, but died earlier than other groups. HIV group status was the only variable predicting microgliosis over large frontal regions. In contrast, in the A\(\upbeta\) plaque microenvironment, APOE \(\upvarepsilon\)4 status and sex were dominant predictors of glial infiltrates, with smaller contributions of HIV status. Cognition correlated with large-scale microgliosis in HIV-D, but not HIV-U, individuals. In this autopsy cohort, over large regions of cortex, HIV status predicts microgliosis, whereas in the A\(\upbeta\) plaque microenvironment, traditional risk factors of AD (APOE \(\upvarepsilon\)4 and sex) are stronger determinants. While microgliosis does not predict neurodegenerative protein deposition, it does predict cognition in HIV-D. Increased neuroinflammation does not initiate amyloid deposition in a younger group with enhanced genetic risk. However, once A\(\upbeta\) deposits are established, APOE \(\upvarepsilon\)4 predicts increased plaque-associated inflammation.

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Title: Frontal lobe microglia, neurodegenerative protein accumulation, and cognitive function in people with HIV
Authors: Jacinta Murray
Gregory Meloni
Etty P. Cortes
Ariadna KimSilva
Michelle Jacobs
Alyssa Ramkissoon
John F. Crary
Susan Morgello
Publication date: 01-12-2022
Publisher: BioMed Central
Keywords: Human Immunodeficiency Virus
Alzheimer's Disease
Alzheimer's Disease
Published in: Acta Neuropathologica Communications / Issue 1/2022
Electronic ISSN: 2051-5960
DOI: https://doi.org/10.1186/s40478-022-01375-y

Keynote webinar | Spotlight on medication adherence

Springer Medicine

Frontal lobe microglia, neurodegenerative protein accumulation, and cognitive function in people with HIV

Abstract

Keynote webinar | Spotlight on medication adherence

Springer Medicine

Abstract

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