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

TitleAlterations in brain TREM2 and Amyloid-β levels are associated with neurocognitive impairment in HIV-infected persons on antiretroviral therapy.
Publication TypeJournal Article
Year of Publication2018
AuthorsFields, JAdam, Spencer, B, Swinton, M, Qvale, EMartine, Marquine, MJ, Alexeeva, A, Gough, S, Soontornniyomkij, B, Valera, E, Masliah, E, Achim, CL, Desplats, P
JournalJ Neurochem
Date Published08/2018
ISSN1471-4159
KeywordsInternal
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/.

DOI10.1111/jnc.14582
Alternate JournalJ. Neurochem.
PubMed ID30152135
Grant ListMH105319 / / 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