# Utilizing Single-nucleus RNA-sequencing to Investigate the Cell-Type Specific Effects of APOE4 Expression in an AD-vulnerable Brain Region

> **NIH NIH R03** · COLUMBIA UNIVERSITY HEALTH SCIENCES · 2020 · $162,000

## Abstract

Project Summary
Possession of the ɛ4 allele of apolipoprotein E (APOE) is the major genetic risk factor for late onset Alzheimer’s
disease (AD), although the direct cause remains a source of debate. While much research has focused on the
association between APOE4 and Aβ pathology, there is significant evidence that APOE4 expression effects a
wide-array of important pathways in the brain that are independent of Aβ, including my own work showing the
effects of APOE4 expression on neuronal hyperactivity, endosomal-lysosomal dysregulation and bioenergetics
deficits in AD-vulnerable brain regions. In order to expand on this work and to gain a more comprehensive picture
of APOE4’s effects in individual cell populations in both mice and humans, I propose to perform single-nucleus
RNA-sequencing on entorhinal cortex (EC) tissues from middle-aged mice and humans expressing APOE4 vs.
APOE3. Data generated from this sequencing strategy will be robustly analyzed using modern bioinformatics
techniques, and gene and pathway hits will be further validating using molecular biology approaches. As APOE4
is the most important genetic determinant of late-onset AD, discovery of cell-type specific effects of APOE4 on
previously identified or novel pathways will greatly increase our knowledge of how late-onset AD develops and
has the potential to uncover new therapeutic strategies for preventing or treating AD, especially among APOE4
carriers.

## Key facts

- **NIH application ID:** 10126136
- **Project number:** 3R03AG063278-02S1
- **Recipient organization:** COLUMBIA UNIVERSITY HEALTH SCIENCES
- **Principal Investigator:** Tal Nuriel
- **Activity code:** R03 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $162,000
- **Award type:** 3
- **Project period:** 2019-05-15 → 2022-01-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10126136

## Citation

> US National Institutes of Health, RePORTER application 10126136, Utilizing Single-nucleus RNA-sequencing to Investigate the Cell-Type Specific Effects of APOE4 Expression in an AD-vulnerable Brain Region (3R03AG063278-02S1). Retrieved via AI Analytics 2026-06-11 from https://api.ai-analytics.org/grant/nih/10126136. Licensed CC0.

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