# Epigenomic, transcriptional and cellular dissection of Alzheimer's variants

> **NIH NIH R01** · MASSACHUSETTS INSTITUTE OF TECHNOLOGY · 2021 · $1,552,886

## Abstract

Abstract
The search for effective treatments for Alzheimer's disease (AD), the leading cause of late-onset dementia,
has proven challenging. While recent successes in identifying more than a dozen new genes contributing to
late-onset or sporadic AD (sAD) have generated considerable excitement in AD research, it is clear from large
population studies including GWAS and whole-exome sequencing projects that many single nucleotide
polymorphisms (SNPs) contributing to elevated sAD risk reside in non-coding intragenic or regulatory regions.
The biological significance of these noncoding SNPs with respect to sAD pathogenesis is not clear. In the
current application, we propose a scalable discovery platform for discerning which AD risk SNPs are
associated with functional enhancers in specific neural cell types derived from human induced stem cells
(hIPSCs). These hIPSCs, created from fibroblasts of sAD patients with a wealth of phenotypes that clearly lead
to AD heterogeneity, will enable us to obtain a high-resolution map of AD risk SNPs associated with enhancers
and their putative target genes in varied cell types. We will utilize CRISPR/Cas9/dCas9 technologies to directly
determine the cell biological consequences of these AD risk genomic variants via 2D and 3D cytosystems. Our
comprehensive strategy will identify novel genetic elements and unexpected regulatory pathways contributing
to AD pathogenesis and progression that will lead to new therapeutic avenues.

## Key facts

- **NIH application ID:** 10207445
- **Project number:** 5R01AG058002-05
- **Recipient organization:** MASSACHUSETTS INSTITUTE OF TECHNOLOGY
- **Principal Investigator:** BRADLEY T. HYMAN
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $1,552,886
- **Award type:** 5
- **Project period:** 2018-06-15 → 2022-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10207445

## Citation

> US National Institutes of Health, RePORTER application 10207445, Epigenomic, transcriptional and cellular dissection of Alzheimer's variants (5R01AG058002-05). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10207445. Licensed CC0.

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