CSF biomarkers of monocyte activation and chemotaxis correlate with magnetic resonance spectroscopy metabolites during chronic HIV disease.

TitleCSF biomarkers of monocyte activation and chemotaxis correlate with magnetic resonance spectroscopy metabolites during chronic HIV disease.
Publication TypeJournal Article
Year of Publication2015
AuthorsAnderson, AM, Fennema-Notestine, C, Umlauf, A, Taylor, MJ, Clifford, DB, Marra, CM, Collier, AC, Gelman, BB, McArthur, JC, J McCutchan, A, Simpson, DM, Morgello, S, Grant, I, Letendre, SL
Corporate AuthorsCHARTER Group
JournalJ Neurovirol
Volume21
Issue5
Pagination559-67
Date Published2015 Oct
ISSN1538-2443
Abstract

Human immunodeficiency virus (HIV)-associated neurocognitive disorders (HAND) persist despite combination antiretroviral therapy (cART), supporting the need to better understand HIV neuropathogenesis. Magnetic resonance spectroscopy (MRS) of the brain has demonstrated abnormalities in HIV-infected individuals despite cART. We examined the associations between MRS metabolites and selected cerebrospinal fluid (CSF) biomarkers reflecting monocyte/macrophage activation and chemotaxis. A multicenter cross-sectional study involving five sites in the USA was conducted. The following CSF biomarkers were measured: soluble CD14 (sCD14), monocyte chemotactic protein-1 (MCP-1), interferon inducible protein 10 (IP-10), and stromal cell-derived growth factor 1 alpha (SDF-1α). The following MRS metabolites were measured from basal ganglia (BG), frontal white matter (FWM), and frontal gray matter (FGM): N-acetylaspartate (NAA), myo-inositol (MI), choline (Cho), and creatine (Cr). CSF biomarkers were compared to absolute MRS metabolites as well as metabolite/Cr ratios using linear regression. Eighty-three HIV-infected individuals were included, 78 % on cART and 37 % with HAND. The most robust positive correlations were between MCP-1 and Cho in BG (R (2) 0.179, p < 0.001) as well as MCP-1 and MI in FWM (R (2) 0.137, p = 0.002). Higher Cr levels in FWM were associated with MCP-1 (R (2) 0. 075, p = 0.01) and IP-10 (R (2) 0.106, p = 0.003). Comparing biomarkers to MRS metabolite/Cr ratios impacted some relationships, e.g., higher sCD14 levels were associated with lower Cho/Cr ratios in FGM (R (2) 0.224, p < 0.001), although higher MCP-1 levels remained associated with Cho/Cr in BG. These findings provide evidence that monocyte activation and chemotaxis continue to contribute to HIV-associated brain abnormalities in cART-treated individuals.

DOI10.1007/s13365-015-0359-6
Alternate JournalJ. Neurovirol.
PubMed ID26069183
Grant ListK24 MH097673 / MH / NIMH NIH HHS / United States
N01 MH022005 / MH / NIMH NIH HHS / United States
P30 MH062512 / MH / NIMH NIH HHS / United States