# Single-cell Epigenome Analysis of the Alzheimer's Disease Brain

> **NIH NIH R44** · EPIGENOME TECHNOLOGIES, INC. · 2024 · $995,100

## Abstract

Project Summary
Late onset AD (LOAD) is a heterogeneous disease that involves complex interactions between genetic,
epigenetic, and environmental risk factors. Genome-wide association studies (GWAS) have identified several
thousand sequence variants linked to increased or decreased risk of AD, most of which are noncoding. The
current paradigm posits that noncoding variants contribute to disease etiology by perturbing transcriptional
regulation in disease-relevant cell types, while environmental risk factors contribute to pathogenesis in part via
alterations to the epigenome. However, a lack of maps and tools to explore gene activities and their
transcriptional regulation at cellular resolution in the brain has presented a major bottleneck to the functional
interpretation of noncoding AD risk variants. In prior work, we applied Droplet Paired-Tag multi-omic profiling of
transcription and histone post-translational modification to post-mortem AD and control parietal cortex,
demonstrating its capacity to profile cellular epigenetics and transcription from bulk samples. This technology
has garnered significant interest through our early-access program. In the proposed study, we will develop a
manufacturing quality management system incorporating references and reference measurements for the
production of Droplet Paired-Tag Kits. We will optimize our protocols specifically on post-mortem AD and
healthy brain tissue from hippocampus, white matter, and cerebellum, as well as on peripheral blood; and
further optimize Droplet Paired-Tag for application to sorted nuclear populations. We will publish the resulting
data as a comprehensive cellular encyclopedia of DNA elements. If successful, the research would catalyze
the study of the epigenetics of AD, and enable the widespread application of next-generation multi-omic assays
to AD and other neurological diseases.

## Key facts

- **NIH application ID:** 11006999
- **Project number:** 2R44AG079691-02
- **Recipient organization:** EPIGENOME TECHNOLOGIES, INC.
- **Principal Investigator:** Christopher Hartl
- **Activity code:** R44 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $995,100
- **Award type:** 2
- **Project period:** 2022-09-30 → 2026-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/11006999

## Citation

> US National Institutes of Health, RePORTER application 11006999, Single-cell Epigenome Analysis of the Alzheimer's Disease Brain (2R44AG079691-02). Retrieved via AI Analytics 2026-05-26 from https://api.ai-analytics.org/grant/nih/11006999. Licensed CC0.

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