# Molecular Mechanisms of Chromatin Remodeling Proteins in Alzheimers Disease

> **NIH NIH R01** · RUTGERS, THE STATE UNIV OF N.J. · 2020 · $390,000

## Abstract

ABSTRACT
Sporadic Alzheimer’s disease (AD) is an age-dependent neurodegenerative disorder characterized by
progressive cognitive dysfunction and memory loss. Pathogenic β-amyloid (Aβ) plaques are a hallmark of AD,
starting first in the hippocampus before spreading to other parts of the brain. Initial research has primarily
focused on how Aβ aggregates are formed. Despite progress made in understanding progression of AD
pathology, fundamental questions remain about what molecular determinants contribute to the onset of AD.
Age-dependent genomic changes likely play a role in AD but the molecular players involved have yet to be
defined. We show that Chd4, a nucleosome repositioning enzyme, dramatically decreases expression with age
in pyramidal neurons of the hippocampus. We propose that Chd4 deletion mimics the epigenomic landscape of
old neurons to accelerate the onset of AD pathology. The goal of the proposal is to address the function of
Chd4 in the context of AD. We will use tools in single-cell transcriptomics and super-resolution microscopy to
determine the molecular changes that occur in pyramidal neurons (Aim1) and the composition of synaptic
proteins as well as the integrity of neuronal circuits in the hippocampus (Aim2) after deleting Chd4. We will also
determine if Aβ plaques and memory loss are observed in animals lacking Chd4 (Aim3).

## Key facts

- **NIH application ID:** 10123370
- **Project number:** 3R01DC015000-05S1
- **Recipient organization:** RUTGERS, THE STATE UNIV OF N.J.
- **Principal Investigator:** Kelvin Y. Kwan
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $390,000
- **Award type:** 3
- **Project period:** 2016-05-15 → 2022-04-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10123370

## Citation

> US National Institutes of Health, RePORTER application 10123370, Molecular Mechanisms of Chromatin Remodeling Proteins in Alzheimers Disease (3R01DC015000-05S1). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10123370. Licensed CC0.

---

*[NIH grants dataset](/datasets/nih-grants) · CC0 1.0*