# Cell type influence on exosome signaling and early pathologic signatures in Alzheimers disease

> **NIH NIH R56** · SCRIPPS RESEARCH INSTITUTE, THE · 2020 · $887,070

## Abstract

Alzheimer’s Disease (AD) is characterized by selective loss of synapses, resulting in decline of cognitive
function. The pathology of AD is increasingly recognized to involve neuronal interactions with other brain cell
types, notably microglia and astrocytes. Extracellular vesicles (EVs) are secreted by all cells in the brain, and
carry protein, lipid and RNA cargo. EVs have the capacity to signal from donor to recipient cells within brain
tissue and modify cell functions, as shown in cancers and multiple neurological diseases. EV propagation of
pathologic proteins between cells in the brain is a strong candidate mechanism underlying at least some
aspects of AD pathology, suggesting that distinct EV cargos may not only serve as biomarkers for disease but
also directly induce vulnerability to or protection from pathologic disease states. Yet, little is known about EV
cargo diversity and bioactivity, in particular whether EV cargos and signaling bioactivity vary by cell type,
physiological state or genetic background of EV donor and recipient cells. To overcome these barriers, we
propose to use iPSCs and direct reprogramming to generate human neurons, astrocytes and microglia from
iPSCs that vary by their AD-related genetic background. We will then precisely define the EV cargos from
these cell types using state-of-the-art proteomic and RNA-Seq methods. In parallel, we will address the
functional consequence of EV diversity with two sensitive readouts of EV signaling pertaining to AD pathology:
neuronal synaptic imaging, and transcriptomic profiling. These collaborative studies will generate critical
insights into the relationship between predicted susceptibilities to AD and EV cargo diversity, EV bioactivity and
AD-related functional changes in neurons. Results of these studies will produce a novel cell-type based
proteomic and RNA catalog of EV diversity, identify candidate biomarkers to test in human AD studies and
uncover candidate pathologic and protective mechanisms linked to specific genetic risks for late onset AD.

## Key facts

- **NIH application ID:** 10233657
- **Project number:** 1R56AG062618-01A1
- **Recipient organization:** SCRIPPS RESEARCH INSTITUTE, THE
- **Principal Investigator:** Kristin Kay Baldwin
- **Activity code:** R56 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $887,070
- **Award type:** 1
- **Project period:** 2020-09-15 → 2022-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10233657

## Citation

> US National Institutes of Health, RePORTER application 10233657, Cell type influence on exosome signaling and early pathologic signatures in Alzheimers disease (1R56AG062618-01A1). Retrieved via AI Analytics 2026-06-01 from https://api.ai-analytics.org/grant/nih/10233657. Licensed CC0.

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