Individuals with HIV infection on suppressive antiretroviral therapy continue to have elevated rates of cognitive impairment. Finding an objective, inexpensive biomarker for cognitive impairment in fluids such as plasma and cerebrospinal fluid (CSF) or neuroimaging would be useful to diagnose worsening impairment and follow with treatment. While there have been many markers suggested for increasing peripheral inflammation, this activation does not always correlate with impairment. Exosomes are spherical vesicles that encapsulate cellular proteins, mRNAs and miRNAs from the cytoplasm of the parent cell. Exosomes are shed into the extracellular space by cells under normal and pathological conditions. They are a form of cell-to-cell communication and their content often mimics the parent cell. We demonstrate that we can isolate plasma exosomes and capture by immunoadsorption, neuron-derived exosomes (NDE). We show that the total number of NDE from HIV-infected subjects is decreased compared to uninfected controls. We also show an increase in high mobility group box 1 (HMGB1) protein, an alarmin that signals cellular stress and damage, in all subjects with mild cognitive impairment, including several impaired subjects without HIV infection. We further demonstrate that the number of NDE have a significant positive correlation with increasing age in HIV+ subjects, unlike uninfected controls. We hypothesize that plasma NDE will have cargo that correlates with increasing cognitive impairment in HIV infection. We also posit that normal aging will influence the exosome cargo. We propose to characterize the exosome protein cargo using mass spectrometry and identify targets that parallel neuronal cell health in normal aging and increasing cognitive impairment in HIV-infection. This allows for a noninvasive, inexpensive technique to monitor brain health and response to therapy. !
Individuals with HIV-1 infection continue to have mild cognitive disorders as well as low levels of chronic peripheral activation. Exosomes are bodies that bleb from the surface of most cells and carry some of the parent cellular cargo. We show that we can isolate exosomes in the blood that come from neurons in the brain. By looking at the contents in these neuron-derived exosomes, we hope to identify biomarkers that correlate with cognitive impairment and neuron health.
| Hu, Guoku; Yelamanchili, Sowmya; Kashanchi, Fatah et al. (2017) Proceedings of the 2017 ISEV symposium on ""HIV, NeuroHIV, drug abuse, & EVs"". J Neurovirol 23:935-940 |
| Sun, Bing; Dalvi, Pranjali; Abadjian, Linda et al. (2017) Blood neuron-derived exosomes as biomarkers of cognitive impairment in HIV. AIDS 31:F9-F17 |
