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- Title
Alterations in brain TREM2 and Amyloid‐β levels are associated with neurocognitive impairment in HIV‐infected persons on antiretroviral therapy.
- Authors
Fields, Jerel Adam; Swinton, Mary; Qvale, Emma Martine; Marquine, María J.; Gough, Sarah; Soontornniyomkij, Benchawanna; Achim, Cristian L.; Spencer, Brian; Alexeeva, Arina; Valera, Elvira; Masliah, Eliezer; Desplats, Paula
- 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 science badges: This article has received a badge for *Open Materials* because it provided all relevant information to reproduce the study in the manuscript. The complete Open Science Disclosure form for this article can be found at the end of the article. More information about the Open Practices badges can be found at https://cos.io/our-services/open-science-badges/. The HIV‐associated neurocognitive disorders (HAND) remain a significant problem despite effective antiretrviral therapy; however, the mechanisms underlying the neuropathogeneisis of HAND are not well understood. In this manuscript, we describe alterations in the levels of TREM2 and Aβ in brains of cases diagnosed with minor neurocognitive disorders (MND) compared to brains from cognitively normal (CN) HIV+ cases. (A) In HIV+ cases that were diagnosed as CN, we identified high levels of TREM2 in membrane‐enriched fractions, increased TREM2 colocalization with the microglial marker IBA1, and lower levels of Aβ when compared to (B) MND cases, in which, the levels of TREM2 were increased in soluble‐enriched fractions and decreased in membrane‐enriched fractions, levels of Aβ were increased, and TREM2 signal associated with IBA1‐positive cells was reduced compared to CN cases. These data may indicate that TREM2 can be a useful biomarker for HAND progression in some individuals and that altered levels of TREM2 may play a role in the neuropathogenesis of HAND. Open Science: This manuscript was awarded with the Open Materials Badge. For more information see: https://cos.io/our-services/open-science-badges/
- Subjects
HIV; AMYLOID beta-protein; TUMOR necrosis factors; MICROGLIA; HISPANIC Americans
- Publication
Journal of Neurochemistry, 2018, Vol 147, Issue 6, p784
- ISSN
0022-3042
- Publication type
Article
- DOI
10.1111/jnc.14582