# Investigation of impaired neural stem cell activation in Alzheimer's Disease

> **NIH NIH R01** · BUCK INSTITUTE FOR RESEARCH ON AGING · 2024 · $462,646

## Abstract

PROJECT SUMMARY
Alzheimer’s Disease (AD) is a devastating neurodegenerative disease that causes severe atrophy in the
hippocampal area. The dentate gyrus of the mammalian hippocampus harbors populations of quiescent neural
stem cells (NSCs) that can re-enter the cell cycle and differentiate into functional excitatory neurons. This
process of neurogenesis supports learning and memory functions, as well as healthy mood regulation.
However, in aging and AD, levels of neurogenesis sharply decline, and work in rodents has demonstrated a
functional link between levels of neurogenesis and cognitive performance. Although quiescent NSCs are the
source of new neurons, the current understanding of how these cells are impacted in AD is extremely limited.
Preliminary work shows that quiescent NSCs are defective in a mouse model of AD. Moreover, these cells are
particularly vulnerable to damage during aging, which is the greatest risk factor for AD. This proposal takes an
integrated, multiomics approach to address the critical question of how the quiescent pool is affected in AD.
Using a well-established mouse model and human tissue, specific Aim 1 will define the transcriptomic and
epigenomic changes at the single cell level in AD. Work in Aim 2 will employ metabolomics to fully elucidate
the metabolic changes that occur in AD. Lastly, Aim 3 will use a functional transcriptomics screen targeting
central pathways in quiescent NSCs to identify how these cells are selectively vulnerable in AD. Together this
work will result in a comprehensive understanding of how dormant NSCs are affected in a mouse model of AD
as well as in human tissue. This study will provide key data to the neurodegeneration community that can be
leveraged for functional studies and the development of interventions to prevent, treat and even cure
neurodegeneration in the long term.

## Key facts

- **NIH application ID:** 10939258
- **Project number:** 7R01AG076933-03
- **Recipient organization:** BUCK INSTITUTE FOR RESEARCH ON AGING
- **Principal Investigator:** Ashley E Webb
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $462,646
- **Award type:** 7
- **Project period:** 2022-06-01 → 2027-03-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10939258

## Citation

> US National Institutes of Health, RePORTER application 10939258, Investigation of impaired neural stem cell activation in Alzheimer's Disease (7R01AG076933-03). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10939258. Licensed CC0.

---

*[NIH grants dataset](/datasets/nih-grants) · CC0 1.0*