Using neuronal extracellular vesicles and machine learning to predict cognitive deficits in HIV

Our objective was to predict HIV-associated neurocognitive disorder (HAND) in HIV-infected people using plasma neuronal extracellular vesicle (nEV) proteins, clinical data, and machine learning. We obtained 60 plasma samples from 38 women and 22 men, all with HIV infection and 40 with HAND. All underwent neuropsychological testing. nEVs were isolated by immunoadsorption with neuron-specific L1CAM antibody. High-mobility group box 1 (HMGB1), neurofilament light (NFL), and phosphorylated tau-181 (p-T181-tau) proteins were quantified by ELISA. Three different computational algorithms were performed to predict cognitive impairment using clinical data and nEV proteins. Of the 3 different algorithms, support vector machines performed the best. Applying 4 different models of clinical data with 3 nEV proteins, we showed that selected clinical data and HMGB1 plus NFL best predicted cognitive impairment with an area under the curve value of 0.82. The most important features included CD4 count, HMGB1, and NFL. Previous published data showed nEV p-T181-tau was elevated in Alzheimer's disease (AD), and in this study, p-T181-tau had no importance in assessing HAND but may actually differentiate it from AD. Machine learning can access data without programming bias. Identifying a few nEV proteins plus key clinical variables can better predict neuronal damage. This approach may differentiate other neurodegenerative diseases and determine recovery after therapies are identified.