# Identification and Characterization of Cell-Specific Transposable Elements Implicated on Alzheimer Disease and Healthy Aging

> **NIH NIH R01** · WASHINGTON UNIVERSITY · 2024 · $1,809,944

## Abstract

Abstract
Alzheimer disease (AD) is the most common form of dementia and neurodegeneration affecting more than 5
million Americans with no current effective treatment. Several Mendelian mutations and risk variants have
been identified. We and others have shown that AD is associated with changes in brain cell proportion and
transcriptomic changes, some of them are also cell specific. Additionally, the latest genetic studies implicate
cell-specific pathogenic events that lead to disease. Pathogenic variants in APP, PSEN1 and PSEN2 affects
APP processing leading to Aβ aggregates and neuronal death. Genetic variants in TREM2 and MS4A modify
AD risk by affecting microglia activity. To fully understand and characterize the role of transposable elements
(TE) in AD pathogenesis there is a need to novel and multidisciplinary approaches. Here we will combine novel
genomic approaches in human brain tissues, direct converted neurons and iPSC-derived microglia (iMGL) to
identify cell-specific TE and downstream (chromatin accessibility, transcription) changes implicated in AD. We
will leverage a large and unique resources of human brain samples and fibroblast from individuals with
mutations in APP, PSEN1, PSEN2, as well as risk variants in TREM2, MS4A or APOE. We will also use the
direct converted neurons and iMGL, together with new genomic editing approaches to target and characterize
the mechanism by which TE contribute to disease.

## Key facts

- **NIH application ID:** 10865118
- **Project number:** 5R01AG078964-03
- **Recipient organization:** WASHINGTON UNIVERSITY
- **Principal Investigator:** Carlos Cruchaga
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $1,809,944
- **Award type:** 5
- **Project period:** 2022-08-15 → 2027-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10865118

## Citation

> US National Institutes of Health, RePORTER application 10865118, Identification and Characterization of Cell-Specific Transposable Elements Implicated on Alzheimer Disease and Healthy Aging (5R01AG078964-03). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10865118. Licensed CC0.

---

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