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Published on: September 19, 2010
Plasma soluble CD163 is associated with postmortem brain pathology in human immunodeficiency virus infection
Alex K Bryant1, David J Moore, Tricia H Burdo
1aHIV Neurobehavioral Research Program bDepartment of Psychiatry, University of California San Diego, La Jolla,California cDepartment of Neuroscience, Lewis Katz School of Medicine, Temple University, Philadelphia, Pennsylvania dDepartment of Biology, Boston College, Chestnut Hill, Massachusetts eDepartment of Pathology fDepartment of Neurosciences, University of California San Diego, La Jolla gDepartment of Neurology, University of California Los Angeles, Los Angeles, California, USA.
Objective:
Higher plasma soluble cluster of differentiation (CD)163 (sCD163), shed by monocytes and macrophages, correlates with neurocognitive impairment in HIV infection. We hypothesized that higher antemortem plasma or cerebrospinal fluid (CSF) 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 CSF (n = 32) samples from 74 HIV-seropositive 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, synaptophysin), microgliosis [human leukocyte antigen DR (HLA-DR), ionized calcium-binding adaptor molecule 1], astrocytosis (glial fibrillary acidic protein), and impaired protein clearance (β-amyloid) in frontal cortex, hippocampus, putamen, and internal capsule. Multivariable least-squares regression was used to evaluate the association between plasma or CSF sCD163 and histological measures, correcting for multiple comparisons.
Results:
Higher plasma sCD163 was associated with lower microtubule-associated protein 2 in frontal cortex [B = -0.23, 95% confidence interval (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 synaptophysin 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). CSF sCD163 was not associated with any histological measure (P > 0.05).
Conclusion:
Higher plasma sCD163 in life is associated with greater synaptodendritic damage and microglial activation in cortical and subcortical brain regions.
Insights
Higher levels of soluble CD163 (sCD163) in blood predict increased brain damage and microglial activation in individuals with HIV. This finding links a specific biomarker to neurodegeneration in HIV infection.
Area of Science:
- Neuroscience
- Immunology
- Infectious Diseases
Background:
- Soluble cluster of differentiation (CD)163 (sCD163), a marker shed by monocytes and macrophages, is linked to neurocognitive impairment in HIV.
- Understanding the relationship between sCD163 and neuropathological changes in HIV is crucial for identifying disease mechanisms.
Purpose of the Study:
- To investigate the association between antemortem plasma or cerebrospinal fluid (CSF) sCD163 levels and postmortem measures of neurodegeneration and microgliosis in HIV-seropositive individuals.
Main Methods:
- A retrospective study analyzed plasma and CSF samples from 74 HIV-positive participants.
- Postmortem brain tissue was examined for markers of synaptodendritic damage, microgliosis, astrocytosis, and impaired protein clearance.
- Multivariable regression was used to assess the correlation between sCD163 levels and histological findings.
Main Results:
- Elevated plasma sCD163 correlated with reduced microtubule-associated protein 2 and synaptophysin in specific brain regions, indicating synaptodendritic damage.
- Higher plasma sCD163 was also associated with increased human leukocyte antigen DR (HLA-DR) in the putamen, suggesting microglial activation.
- No significant associations were found between CSF sCD163 levels and histological measures.
Conclusions:
- Higher plasma sCD163 levels measured during life are associated with increased synaptodendritic damage and microglial activation in brain regions of individuals with HIV.
- These findings highlight plasma sCD163 as a potential biomarker for HIV-associated neurodegeneration.

