# Plasma neuronal-derived exosomes are biomarkers of HIV cognitive impairment

> **NIH NIH R01** · NORTHERN CALIFORNIA INSTITUTE/RES/EDU · 2020 · $543,233

## Abstract

Cognitive impairment in chronic well-controlled HIV infection continues to affect from 30%-60%
of individuals. Mechanisms are still unknown but probably associated with continued
neuroinflammation. Biomarkers for cognitive impairment have been inconsistent although
neuroimaging has emerged as a possibility. Unfortunately, imaging is expensive with limited
access. Exosomes are small microvesicles shed from most all cells under normal and pathologic
conditions. The cellular cargo packaged into exosomes can represent the state of the parent cell.
We have isolated neuron-derived exosomes (NDE) in plasma using a 2-step isolation procedure
and a cell surface neuron specific antibody. We have shown in a recently completed R21 using
mass spectroscopy that NDE are rich in over 50 neuronal proteins. In addition, using proximity
extension analysis (PEA) for neurology biomarkers, we identified an additional 28 proteins that
were present. At least 7 proteins were statistically significantly differentially expressed in HIV
infection alone, neurocognitive impairment in HIV+ women versus men and 1 protein that was
significantly correlated with age and impairment. Several NDE proteins correlate with cognitive
domains and several differentiate HIV cognitive impairment from Alzheimer’s disease. Our
overall hypothesis is that NDE can be used to diagnose cognitive impairment in HIV infection
and that men and women have different proteins in NDE that will influence diagnosis and
treatment. We further plan to differentiate mild cognitive impairment with that associated with a
pre-Alzheimer’s mild cognitive impairment (MCI) diagnosis. To test this hypothesis, we propose
the following Specific Aims: (1) Select and verify a set of neuronal exosome proteins that predict
and diagnose HIV cognitive impairment with aging in women and men, (2) Determine whether
neuronal exosome cargo can differentiate HIV-associated cognitive impairment from mild
MCI/Alzheimer’s disease (3) Correlate HIV NDE protein targets and cognitive domains
associated with neuroimaging markers of injury and (4) Establish a rapid ultrasensitive assay
using verified neuronal exosome target proteins for diagnosis of HIV cognitive impairment in a
longitudinal cohort. We will utilize a multidisciplinary approach that includes basic research of
protein targets correlated with cognitive domains and clinical diagnosis using neuroimaging
correlation with selected biomarker proteins. These results will have major impact on treatment
and cure of HIV in the brain as fluid biomarkers are discovered and the health of the neuron can
be assessed in “real time.”

## Key facts

- **NIH application ID:** 9927404
- **Project number:** 1R01MH121121-01A1
- **Recipient organization:** NORTHERN CALIFORNIA INSTITUTE/RES/EDU
- **Principal Investigator:** Lynn PULLIAM
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $543,233
- **Award type:** 1
- **Project period:** 2020-05-15 → 2025-02-28

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9927404

## Citation

> US National Institutes of Health, RePORTER application 9927404, Plasma neuronal-derived exosomes are biomarkers of HIV cognitive impairment (1R01MH121121-01A1). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/9927404. Licensed CC0.

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