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Blood neuron-derived exosomes as biomarkers of cognitive impairment in HIV

Sun, Binga; Dalvi, Pranjalia; Abadjian, Lindaa; Tang, Norinaa; Pulliam, Lynna,b

doi: 10.1097/QAD.0000000000001595

Objective: To investigate proteins associated with neuronal damage in plasma neuron-derived exosomes (NDE) of HIV-infected study participants as a liquid biomarker for cognitive impairment.

Methods: Plasma NDE were isolated using precipitation and immunoadsorption with antibody to a cell surface-specific neuronal marker. Total exosomes and NDE were enumerated, characterized, and proteins extracted and targets quantified by ELISA.

Results: Plasma NDE from 23 HIV seropositive individuals of which 11 had mild cognitive impairment, and 12 HIV seronegative controls of which three had cognitive impairment were isolated. NDE were enriched for the neuronal markers neurofilament light (NF-L) and synaptophysin (SYP). Neuropsychologically impaired individuals had fewer NDE compared with neuropsychologically normal study participants. NDE from neuropsychologically impaired study participants had significantly higher levels of high-mobility group box 1 (HMGB1), NF-L, and amyloid β proteins compared with neuropsychologically normal individuals. NDE HMGB1 protein significantly decreased with age in HIV-infected individuals.

Conclusion: Plasma NDE were altered in several ways in HIV infection. Elevated HMGB1, NF-L, and amyloid β proteins could distinguish cognitive impairment. NDE contents reflect neuronal health in ‘real time’ and may be useful for following cognitive impairment and response to therapy in HIV infection.

aVeterans Affairs Medical Center

bDepartments of Laboratory Medicine and Medicine, University of California, San Francisco, California, USA.

Correspondence to Lynn Pulliam, Department of Laboratory Medicine, Veterans Affairs Medical Center, University of California, San Francisco, 4150 Clement St., 113A, San Francisco, CA, USA. Tel: +1 415 221 4810; e-mail:

Received 8 June, 2017

Revised 26 June, 2017

Accepted 3 July, 2017

Copyright © 2017 Wolters Kluwer Health, Inc.