# Illuminating the APOE Locus with Long-Read Sequencing and Targeted Genomics

> **NIH NIH R35** · STANFORD UNIVERSITY · 2023 · $922,482

## Abstract

PROJECT SUMMARY/ABSTRACT
Alzheimer’s disease (AD) is a common, progressive, and ultimately fatal brain disease. Currently approved
treatments provide only minimal symptomatic benefits and do not stop the disease from progressing. The field
is in dire need of novel drug targets which could lead to disease-modifying therapies. The most common
genetic risk factor for AD is the ε4 variant of the apolipoprotein E gene (APOE4). The effect of APOE4 varies
greatly between people of African ancestry and people of European ancestry. The current study—Illuminating
the APOE Locus with Long-Read Sequencing and Targeted Genomics—will apply a new genome sequencing
technology (long-read sequencing) to the study of APOE and several other AD-relevant genes including
ABCA7. Long-read sequencing will be performed on DNA from roughly 2000 African-Americans with AD and
2000 healthy older African-American control subjects as well as DNA from roughly 5000 European-American
AD patients and 5000 European-American controls. A subset of these patients will also have long-read
sequencing of these genes’ RNA derived from white blood cells, fibroblasts, or brain tissue. These analyses
will help us understand how local genetic variants near the APOE4 variant can alter the type or amount of the
APOE4 protein and how this affects risk of AD. Similar analyses will be done on ABCA7 and another 15-20
targeted genes that will be selected just before sequencing begins and following an up-to-date review of the
AD genetics literature. In addition to understanding the local variants regulating a gene and the protein it
produces, long-read sequencing will be useful in detecting large, damaging genetic mutations that are easily
missed with standard whole-genome sequencing. The results will allow for more specific estimates of AD risk
in individuals of diverse ancestral backgrounds and will provide novel targets for drug development.

## Key facts

- **NIH application ID:** 10640191
- **Project number:** 5R35AG072290-03
- **Recipient organization:** STANFORD UNIVERSITY
- **Principal Investigator:** Michael D Greicius
- **Activity code:** R35 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2023
- **Award amount:** $922,482
- **Award type:** 5
- **Project period:** 2021-09-01 → 2026-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10640191

## Citation

> US National Institutes of Health, RePORTER application 10640191, Illuminating the APOE Locus with Long-Read Sequencing and Targeted Genomics (5R35AG072290-03). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10640191. Licensed CC0.

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