# Epigenetic-Genetic Modulations in Aging and Alzheimer's Disease Neurons

> **NIH NIH R01** · UNIV OF MASSACHUSETTS MED SCH WORCESTER · 2021 · $643,399

## Abstract

The current proposal was inspired by our recently applied methodology for whole-genome analysis of
regulatory chromatin landscape and genetic-epigenetic interactions in human brain neurons. We hypothesize
that, during aging, the active chromatin in human cortical neurons is gradually modified in a subset of
chromosomal loci. These chromatin modifications lead to an altered epigenetic state of activity of certain
genes, contributing to vulnerability of aging neurons in brain regions vulnerable to Alzheimer's disease (AD) -
related degeneration signals. We plan to identify these aging-specific neuro-chromatin signatures marked by
modified histones specific for active gene promoters and active gene enhancers. We will apply ChIP-seq
technology for whole-genome analysis of neuronal chromatin extracted from brain regions susceptible to AD
both in a cohort of non-demented individuals stratified by age and in AD patients. We will search whether the
group of genes epigenetically modified in aging and AD neurons is enriched in any gene ontology category and
specific biological pathway. The genes with altered epigenetic signatures will be tested further whether they
overlap with the genetic risk loci for AD and AD-related traits. We suggest that the genes for signal
transducers, especially for genes with stress-response and immune functions, are targets for epigenetic
modifications in aging- neurons underlying AD neurodegeneration. These predictions will be tested in animal
models by direct knockdown of gene activity by a novel type of siRNA therapeutic compounds.

## Key facts

- **NIH application ID:** 10135796
- **Project number:** 5R01AG054712-05
- **Recipient organization:** UNIV OF MASSACHUSETTS MED SCH WORCESTER
- **Principal Investigator:** EVGENY I ROGAEV
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $643,399
- **Award type:** 5
- **Project period:** 2017-09-01 → 2024-03-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10135796

## Citation

> US National Institutes of Health, RePORTER application 10135796, Epigenetic-Genetic Modulations in Aging and Alzheimer's Disease Neurons (5R01AG054712-05). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10135796. Licensed CC0.

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