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.

Abstract

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.