# Exosome Mediated Alterations in Cellular Metabolism in the Pathogenesis and Progression of Alzheimer's Disease

> **NIH NIH R01** · UNIVERSITY OF CALIFORNIA, SAN DIEGO · 2021 · $694,254

## Abstract

7. Project Summary/Abstract
 Alterations in exosome secretion and content have been linked to Alzheimer's disease (AD). These
nanovesicles are abundant in circulation and are being examined as promising blood-based biomarkers of
disease. Importantly, exosomes derived from AD patients and animal models have been shown to carry
pathogenic cargo and can contribute to the spread of neuronal dysfunction. Our preliminary data provide
striking new evidence that key features of early AD pathophysiology, such as mitochondrial dysfunction and
altered cellular metabolism, can be mediated by exosomes derived from AD patients. The proposed study will
test the hypothesis that circulating exosomes mediate systemic changes in cellular metabolism associated with
early stages of AD and contribute to the spread of AD pathology over the long-term progression of disease.
The primary goals of this proposal are: 1) to characterize total, neuron-derived, and astrocyte-derive exosomes
across stages of AD and over the 3 year progression of disease using integrated omics analysis; and 2) to
examine the mechanisms by which exosomes affect cellular metabolism, AD pathology, and cognitive decline
using complementary in vitro, ex vivo, and in vivo approaches.
 The proposed study capitalizes on a unique and timely opportunity to utilize plasma samples from an
ongoing NIA-funded study of participants in the Wake Forest Alzheimer' Disease Center Clinical Core. With the
costs for sample collections, key clinical measures, and human bioenergetic profiling covered by existing
funding, we have a valuable opportunity to advance our understanding of how exosome-mediated intercellular
communication is involved in the onset and spread of AD pathophysiology. The results of this study will provide
new mechanistic insights into mediators of AD pathology and could shift the focus of AD prevention and
therapy to include strategies targeting the detrimental effects of exosome mediated intercellular signaling and
systemic bioenergetic decline. The robust framework of this study will support future research efforts by
advancing novel in vitro and in vivo experimental approaches, and by generating a comprehensive exosome
repository and database linked to an ongoing longitudinal cohort study of AD.

## Key facts

- **NIH application ID:** 10147840
- **Project number:** 5R01AG061805-04
- **Recipient organization:** UNIVERSITY OF CALIFORNIA, SAN DIEGO
- **Principal Investigator:** ANTHONY J MOLINA
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $694,254
- **Award type:** 5
- **Project period:** 2018-09-30 → 2023-04-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10147840

## Citation

> US National Institutes of Health, RePORTER application 10147840, Exosome Mediated Alterations in Cellular Metabolism in the Pathogenesis and Progression of Alzheimer's Disease (5R01AG061805-04). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10147840. Licensed CC0.

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