Alterations in brain TREM2 and Amyloid-β levels are associated with neurocognitive impairment in HIV-infected persons on antiretroviral therapy

Journal of Neurochemistry
Jerel Adam FieldsPaula Desplats

Abstract

Neuroinflammation is a common pathological correlate of HIV-associated neurocognitive disorders (HAND) in individuals on antiretroviral therapy (ART). Triggering receptor expressed on myeloid cells 2 (TREM2) regulates neuroinflammation, clears extracellular Amyloid (A)-β, surveys for damaged neurons, and orchestrates microglial differentiation. TREM2 has not been studied in HIV+ brain tissues. In this retrospective study, we investigated TREM2 expression levels and localization to microglia, Aβ protein levels, and tumor necrosis factor (TNF)-α transcript levels in the frontal cortices of 52 HIV+ decedents. All donors had been on ART; 14 were cognitively normal (CN), 17 had an asymptomatic neurocognitive impairment (ANI), and 21 had a minor neurocognitive disorder (MND). Total TREM2 protein levels were increased in the soluble and decreased in the membrane-enriched fractions of MND brain tissues compared to CN; however, brains from MND Hispanics showed the most robust alterations in TREM2 as well as significantly increased TNF-α mRNA and Aβ levels when compared to CN Hispanics. Significant alterations in the expression of total TREM2 protein and transcripts for TNF-α were not observed in non-Hispanics, despite higher levels of A...Continue Reading

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Jan 12, 2020·Glia·Jonathan Hasselmann, Mathew Blurton-Jones
Jun 4, 2020·Journal of Neurovirology·Audrey C KnightJoseph L Mankowski
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