Alterations in brain TREM2 and Amyloid-β levels are associated with neurocognitive impairment in HIV-infected persons on antiretroviral therapy.
Title | Alterations in brain TREM2 and Amyloid-β levels are associated with neurocognitive impairment in HIV-infected persons on antiretroviral therapy. |
Publication Type | Journal Article |
Year of Publication | 2018 |
Authors | Fields, JA, Spencer, B, Swinton, M, Qvale, EMartine, Marquine, MJ, Alexeeva, A, Gough, S, Soontornniyomkij, B, Valera, E, Masliah, E, Achim, CL, Desplats, P |
Journal | J Neurochem |
Date Published | 08/2018 |
ISSN | 1471-4159 |
Keywords | Internal |
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 Aβ in the non-Hispanic CN group compared to the non-Hispanic MND groups. These findings show that decreased and increased TREM2 in membrane-bound fractions and in soluble-enriched fractions, respectively, is associated with increased Aβ and neuroinflammation in this cohort of HIV+ brains, particularly those identifying as Hispanics. These findings suggest a role for TREM2 in the brain of HIV+ individuals may deserve more investigation as a biomarker for HAND and as a possible therapeutic target. Open Data: Materials are available on https://cos.io/our-services/open-science-badges/ https://osf.io/93n6m/. |
DOI | 10.1111/jnc.14582 |
Alternate Journal | J. Neurochem. |
PubMed ID | 30152135 |
Grant List | MH105319 / / National Institute of Mental Health / MH115819 / / National Institute of Mental Health / AG043394 / / National Institute on Aging / R01 MH105319 / MH / NIMH NIH HHS / United States K23 MH105297 / MH / NIMH NIH HHS / United States R01 AG043384 / AG / NIA NIH HHS / United States U24 MH100928 / MH / NIMH NIH HHS / United States K01 MH115819 / MH / NIMH NIH HHS / United States P30 MH062512 / MH / NIMH NIH HHS / United States |