# Surface Signatures of Neuronal and Glial Extracellular Vesicles

> **NIH NIH UH3** · MESO SCALE DIAGNOSTICS, LLC · 2022 · $895,446

## Abstract

Abstract
 Extracellular vesicles (EVs) are believed to be an important means of cell-to-cell
communication in the central nervous system. Various types of cells in the human brain secrete
EVs, which are each likely to have distinct functions. Studying different types of EVs and their
roles in the healthy brain and in neurological disease requires a reliable means of capturing
these particles from readily accessible body fluids, like blood. Our goal is to develop a new way
to capture specific types of EVs based on the molecules present on their surfaces. Our
hypothesis is that we can use the presence of two or more specific molecules on the surface of
an EV to select EVs secreted by a particular cell type.
 MSD has previously developed efficient and highly sensitive methods for screening EVs
to determine combinations of proteins present on their surfaces. We will use these methods
along with samples provided by our collaborators at the National Institute on Aging to identify
specific surface-marker signatures for each of the four most common types of cells in the central
nervous system.
 We will develop a new approach to capturing EVs with each of these surface marker
signatures. This approach, which will only capture the EVs having all of the targeted surface
markers, should greatly improve the capture specificity, thus addressing one of the main
shortcomings of the existing CNS EV isolation methods. Greater specificity will enable more
targeted studies of the EVs from each CNS cell type than those that are presently performed.
We will use this approach to determine which human biofluids can be a reliable source of EVs
from the central nervous system and to estimate the level of each type of EV in peripheral body
fluids.
 We will also measure the proteins contained within the EVs, something that requires
exceptionally sensitive assays. We recently combined ultrasensitive immunoassays with EV-
specific capture methods to enable accurate measurement of specific EV cargo proteins. We
will assay the EV cargo for proteins specific to each of the four CNS cell types to help confirm
the cellular origin of the isolated EVs. We will also measure known EV-associated biomarkers
of Alzheimer’s disease in patient samples to determine in which EV types they are enriched and
to see whether measuring the biomarker within a particular type of EV might increase its
predictive power.
 Lastly we plan to develop a fully automated version of the EV isolation and cargo protein
assays. This will enable rapid and reliable preparation of EV samples from hundreds of
samples at a time, allowing studies that presently would be either impossible or too time-
consuming to be cost-effective.

## Key facts

- **NIH application ID:** 10460520
- **Project number:** 5UH3MH118167-05
- **Recipient organization:** MESO SCALE DIAGNOSTICS, LLC
- **Principal Investigator:** David Aaron Routenberg
- **Activity code:** UH3 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $895,446
- **Award type:** 5
- **Project period:** 2018-09-19 → 2025-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10460520

## Citation

> US National Institutes of Health, RePORTER application 10460520, Surface Signatures of Neuronal and Glial Extracellular Vesicles (5UH3MH118167-05). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/10460520. Licensed CC0.

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