‘Plasma monocyte-derived extracellular vesicles are associated with neurocognitive impairment in HIV infected individuals.’

Abstract

Abstract Monocytes contribute to the neuropathogenesis of HIV-related cognitive impairment (CI) as they enter the central nervous system and initiate a cascade of neuroinflammatory events. Extracellular vesicles (EVs) are potent vehicles of intercellular signaling and may reflect the state of cells in the brain under healthy and pathological conditions. We measured EVs in plasma from 79 HIV-infected adults enrolled in the Hawaii Aging with HIV Cohort, classified as having either normal cognition (n=16) or CI based on meeting criteria for HIV-Associated Dementia (n=25) or Mild Cognitive Motor Disorder (n=38). We tested whether EV phenotypes differed between those with and without CI. EVs expressing monocyte-associated markers (EVs/μl) were significantly higher in HIV+ donors with CI compared to those without CI: CD14 (819 vs. 118.5, p=0.017), CD4 (261 vs. 45, p=0.001), CD16 (898 vs. 215, p<0.0001), CD163 (1660 vs. 55, p=0.010), and CCR5 (202 vs. 43.5, p=0.009). In addition, increased levels of EVs expressing neural markers were found in HIV+ adults with CI compared to those without CI: MAP2 (531 vs. 103.5, p=0.013), GFAP (1810 vs. 775, p=0.036), and CD200 (1216 vs. 36.5, p=0.005). There was no significant difference between the two groups in age, CD4 count, viral load, and, EVs expressing CD3, CD41a, CD62p, CD63, CCR2 and CD11b. Levels of CD16-expressing EVs negatively correlated with the degree of CI using a composite of 8 neuropsychological (NP) tests to compute a summary NPZ-8 score (r=−0.224, p=0.046). Our findings reveal that EVs expressing monocyte activation and neural damage markers correlate with CI in HIV+ adults. These techniques reveal novel circulating biomarkers of CI, and neuronal pathogenesis markers utilizing peripheral blood.