Use of Neuronal-Enriched Extracellular Vesicles to Distinguish Cognitive Impairment Levels and Sex Differences in...

Cognitive impairment still occurs despite well-controlled HIV but with milder symptoms. People with and without HIV have different neuronal protein changes that may differentiate the asymptomatic neurocognitive impairment (ANI) condition from normal cognition (NPN) and mild neurocognitive disorder (MND). Plasma neuronal-enriched extracellular vesicles (nEVs) were isolated from people with HIV (PWH) with NPN, ANI, or MND, and HIV seronegative controls with NPN (HIV-). Two different platforms were used to delineate protein patterns between sexes and cognitive conditions. When combining results from men and women, the nEV cargo in many cases showed little difference between cognitive conditions. However, when separated, there were different patterns between the sexes for some nEV cargo that distinguished the HIV- groups and HIV+ cognition groups. PWH with NPN had higher nEV toxic proteins compared to individuals without HIV. Women with HIV showed perfect separation between NPN and ANI with Aβ42 and NCAM-1 and perfect separation between ANI and MND with Aβ40 and NCAM-1. Men with HIV with MND had significantly higher NCAM-1 when compared to ANI, and lower GLRX when compared to NPN. This study shows distinct markers for different HIV cognitive categories, many of which differed between men and women.