Date Published:
08/2018

Publication Type:
Journal Article

Authors:

J.A. Fields
B. Spencer
M. Swinton
E.Martine Qvale
M.J. Marquine
A. Alexeeva
S. Gough
B. Soontornniyomkij
E. Valera
E. Masliah
C.L. Achim
P. Desplats

Secondary:
J Neurochem

PMID:
30152135

URL:
https://pubmed.ncbi.nlm.nih.gov/30152135

DOI:
10.1111/jnc.14582

Keywords:
Internal

Abstract:
<p>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 <a href="https://cos.io/our-services/open-science-badges/">https://cos.io/our-services/open-science-badges/</a> <a href="https://osf.io/93n6m/">https://osf.io/93n6m/</a>.</p>