# Single Exosome Technology for Alzheimer's Disease

> **NIH NIH R43** · NUMENTUS TECHNOLOGIES INC. · 2021 · $299,151

## Abstract

PROJECT SUMMARY
 This project responds to the important need for improved diagnostics for Alzheimer’s disease (AD). Existing
methods based on biomarkers such as Ab and tau protein ratios from cerebrospinal fluid (CSF) are useful but
incomplete. Furthermore, CSF sampling requires lumbar puncture and is too expensive for broad screening. A
class of extracellular vesicles (EVs), exosomes, provide an attractive target for AD diagnostics. Exosomes
freely cross the blood-brain barrier and can be readily sampled in peripheral blood, enabling a blood-based
liquid biopsy. Exosomes also provide rich signatures for disease detection, including both proteins and nucleic
acids (mRNA, miRNA, and other non-coding RNAs). The majority of studies on EVs and AD have been
performed with bulk or batch analyses. Bulk analysis has a fundamental limitation because the relatively rare
exosomes specific to the central nervous system (CNS) are easily confounded (swamped) by the exosome
contributions of peripheral cells. To overcome this limitation, we are developing methods for combined
protein/nucleic acid analysis in single exosomes. Our innovative, high-content, high-throughput method is
designed to simultaneously analyze, in one pass, up to 10 potential AD biomarker cargoes in as many as 107
individual, CNS-tagged blood exosomes. These unique capabilities provide multiple advantages over previous
approaches. Our method can rapidly: 1) distinguish and separately analyze both exosomes and other EVs; 2)
discriminate and simultaneously evaluate multiple CNS-specific exosome surface markers, whereas
conventional approaches can only evaluate one CNS-specific surface marker at a time, significantly limiting the
ability to identify exosomes of CNS origin; 3) individually interrogate each and every exosome in a sample for
its cargoes, dramatically raising information content compared to conventional methods where exosome
cargoes must be pooled; and 4) search for unique combinations of biomarkers within unique, CNS-specific
exosomal populations, an impossibility with conventional approaches. We therefore propose the following
stepwise objectives for this Phase I project. First, to optimize the combined protein/nucleic acid analysis of
exosomes produced by human SH-SY5Y cells. Second, to assay exosomes in brain homogenate samples
from rapid autopsies of 40 AD, 40 mild cognitive impairment (MCI), 40 non-AD neurological conditions
(nADneuro) (e.g., Parkinson’s disease, amyotrophic lateral sclerosis), and 40 normal elderly control (NC)
subjects. Third, to assay exosomes in rapid autopsy blood samples from AD, MCI, nADneuro, and NC subjects
that provided brain samples used in Objective 2.
 We anticipate that our novel imaging platform has the potential to become a new research/diagnostic/
prognostic tool for the clinical management of AD or other pathologies in which EV/exosomal analysis could
provide clinically useful information, such as other neurodegenerative diseases, cancer, an...

## Key facts

- **NIH application ID:** 10330840
- **Project number:** 1R43AG074869-01
- **Recipient organization:** NUMENTUS TECHNOLOGIES INC.
- **Principal Investigator:** GREGORY W FARIS
- **Activity code:** R43 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $299,151
- **Award type:** 1
- **Project period:** 2021-09-15 → 2024-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10330840

## Citation

> US National Institutes of Health, RePORTER application 10330840, Single Exosome Technology for Alzheimer's Disease (1R43AG074869-01). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10330840. Licensed CC0.

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