| Publication Abstract Display | | Type: Published Manuscript | | Title: Plasma soluble CD163 is associated with postmortem brain pathology in human immunodeficiency virus infection. | | Authors: Bryant AK, Moore DJ, Burdo TH, Lakritz JR, Gouaux B, Soontornniyomkij V, Achim CL, Masliah E, Grant I, Levine AJ, Ellis RJ | | Year: 2017 | | Publication: AIDS (London, England) | | Volume: 31 Issue: 7 Pages: 973-979 | | Abstract:Higher plasma soluble CD163 (sCD163), shed by monocytes and macrophages, correlates with neurocognitive impairment in human immunodeficiency virus (HIV) infection. We hypothesized that higher antemortem plasma or cerebrospinal fluid sCD163 would be associated with greater postmortem neurodegeneration and/or microgliosis.
DESIGN:
Retrospective, postmortem observational study.
METHODS:
We measured sCD163 levels in antemortem plasma (n = 54) and cerebrospinal fluid (n = 32) samples from 74 HIV participants (median 5 months before death) who donated their brains to research at autopsy. Postmortem, we quantified markers of synaptodendritic damage (microtubule-associated protein 2 [MAP2], synaptophysin [SYP]), microgliosis (HLA-DR, ionized calcium binding adaptor molecule 1), astrocytosis (glial fibrillary acidic protein) and impaired protein clearance (beta-amyloid) in frontal cortex, hippocampus, putamen, and internal capsule. Multivariable least-squares regression was used to evaluate the association between plasma or cerebrospinal fluid sCD163 and histological measures, correcting for multiple comparisons.
RESULTS:
Higher plasma sCD163 was associated with lower MAP2 in frontal cortex (B = -0.23, 95% CI -0.41 to -0.06, p = 0.04), putamen (B = 0.32, 95% CI -0.52 to -0.12, p = 0.02), and hippocampus (B = -0.23, 95% CI -0.35 to -0.10, p = 0.01), and with lower SYP in hippocampus (B = -0.25, 95% CI -0.42 to -0.03, p = 0.02) but not putamen or frontal cortex (p > 0.05). Higher plasma sCD163 was associated with higher HLA-DR in putamen (B = 0.17, 95% CI 0.08 to 0.26, p = 0.008). Cerebrospinal fluid sCD163 was not associated with any histological measure (p > 0.05).
CONCLUSIONS:
Higher plasma sCD163 in life is associated with greater synaptodendritic damage and microglial activation in cortical and subcortical brain regions. |
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