# Dissecting the role of hippocampal exosomes in Alzheimer's disease pathogenesis

> **NIH NIH F31** · WAKE FOREST UNIVERSITY HEALTH SCIENCES · 2022 · $42,113

## Abstract

Summary
Alzheimer’s disease is the most common form of dementia and afflicts 5.8 million individuals in the US alone.
Discovered over 100 years ago, there is still little known about what causes Alzheimer’s disease and more
importantly, no therapies exist to treat, prevent, or slow Alzheimer’s disease progression. Impaired degradation
and clearance of aggregated, toxic proteins is characteristic of Alzheimer’s disease. The release of exosomes
has been suggested as an alternative pathway for cellular clearance. However, exosomes can also carry
amyloid-β, the toxic protein that aggregates to form amyloid plaques, suggesting exosome secretion could also
enhance extracellular spread of pathology. Nevertheless, current Alzheimer’s research has mainly focused on
brain-derived exosomes isolated from circulating blood as potential biomarkers for Alzheimer’s disease.
However, it is unknown whether these blood exosomes mimic the pool of exosomes found in the interstitial
fluid (ISF) of brain regions susceptible to Alzheimer’s disease. Determining the relationship between these two
exosome pools has exciting implications for not only facilitating Alzheimer’s diagnosis but also for
understanding Alzheimer’s pathogenesis. Previous studies have examined exosomes from the extracellular
space of brain tissue, but little is known about exosomes found in vivo in the ISF. In this proposal, I will use a
novel approach to collect exosomes from the hippocampal ISF of unanesthetized, freely moving mice using in
vivo microdialysis. I will then compare the ISF pool of exosomes from APP/PS1 mice, a mouse model of
cerebral amyloidosis, with the ISF from wildtype mice. Moreover, I will investigate how the ISF pool from the
hippocampus differs from the population isolated from the blood. I will also characterize how age, sex, and
amyloid plaque pathology change exosome concentration and composition. It is imperative to examine
alterations in brain ISF exosomes in order to gain more insight into the role of exosomes in Alzheimer’s
pathogenesis and as effective biomarkers of Alzheimer’s disease. This proposal will shed further light on brain-
derived exosomes in blood and examine whether they are accurate pictures of what is going on in the in vivo
brain during Alzheimer’s progression.

## Key facts

- **NIH application ID:** 10474341
- **Project number:** 5F31AG071119-02
- **Recipient organization:** WAKE FOREST UNIVERSITY HEALTH SCIENCES
- **Principal Investigator:** Morgan Pait
- **Activity code:** F31 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $42,113
- **Award type:** 5
- **Project period:** 2021-08-06 → 2023-06-01

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10474341

## Citation

> US National Institutes of Health, RePORTER application 10474341, Dissecting the role of hippocampal exosomes in Alzheimer's disease pathogenesis (5F31AG071119-02). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10474341. Licensed CC0.

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