In:
Journal of Neurochemistry, Wiley, Vol. 147, No. 6 ( 2018-12), p. 784-802
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 ( TREM 2) regulates neuroinflammation, clears extracellular Amyloid (A)‐β, surveys for damaged neurons, and orchestrates microglial differentiation. TREM 2 has not been studied in HIV + brain tissues. In this retrospective study, we investigated TREM 2 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 TREM 2 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 TREM 2 as well as significantly increased TNF ‐α mRNA and Aβ levels when compared to CN Hispanics. Significant alterations in the expression of total TREM 2 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 TREM 2 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 TREM 2 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/ . image
Type of Medium:
Online Resource
ISSN:
0022-3042
,
1471-4159
DOI:
10.1111/jnc.2018.147.issue-6
Language:
English
Publisher:
Wiley
Publication Date:
2018
detail.hit.zdb_id:
2020528-4
SSG:
12
Permalink