# Functional characterization of the Alzheimer's disease Epigenome

> **NIH NIH R00** · J. DAVID GLADSTONE INSTITUTES · 2022 · $107,276

## Abstract

PROJECT SUMMARY / ABSTRACT
 Alzheimer’s disease (AD) manifests as a devastating age-related progressive neurodegeneration. This
neurodegeneration and the concomitant loss of cognitive function plagues more than 44 million individuals
worldwide. Our understanding of the molecular pathogenesis of AD remains incomplete and no therapies exist
to prevent, stop, or cure the associated neurodegeneration. This marks one of the greatest unmet clinical needs
of our time.
 Through decades of research, genome-wide association studies have identified heritable coding and
non-coding mutations that lead to an increased risk of developing AD. Many of these mutations, however, remain
largely under-characterized and their contribution to AD pathogenesis remains unclear. Moreover, it has become
increasingly clear that an individual’s lifetime risk of developing AD is not merely governed by genetics. In
addition, the epigenome, the complement of all of the chemical and physical modifications imposed on DNA that
do not change the underlying sequence, is also thought to play a crucial role. This project aims to define the
epigenetic (Aim 1) and genetic (Aim 2) components of AD through profiling of the open chromatin landscapes
and three-dimensional chromatin interactions in brain regions and primary cell types of patients with and without
AD. These characterizations will identify key AD-related regulatory elements that will be functionally validated
with CRISPR interference tiling assays (Aim 3). Taken together, this project will provide an unprecedented
picture of the AD epigenome, identifying novel aspects of AD pathogenesis and nominating putative avenues for
therapeutic intervention.
 This work will be performed under the co-mentorship of Dr. Howard Chang, an expert in the application
of epigenomics to disease, and Dr. Thomas Montine, a leader in brain aging and AD, at the Stanford University
School of Medicine, a world-class research institution. Aims 1 and 2 will be performed predominantly during the
K99 mentored phase while Aims 3 and 4 will be performed predominantly during the R00 independent phase. If
funded, this award will allow me to pursue a rigorous training plan in neurobiology and age-related
neurodegeneration, enabling me to expand my research in new directions, learn new techniques, and acquire
the knowledge and skills to establish an independent laboratory focused on the epigenetics of AD.

## Key facts

- **NIH application ID:** 10691634
- **Project number:** 3R00AG059918-05S1
- **Recipient organization:** J. DAVID GLADSTONE INSTITUTES
- **Principal Investigator:** Michael Ryan Corces
- **Activity code:** R00 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $107,276
- **Award type:** 3
- **Project period:** 2018-07-15 → 2023-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10691634

## Citation

> US National Institutes of Health, RePORTER application 10691634, Functional characterization of the Alzheimer's disease Epigenome (3R00AG059918-05S1). Retrieved via AI Analytics 2026-05-21 from https://api.ai-analytics.org/grant/nih/10691634. Licensed CC0.

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