# Mechanistic Studies on the Impact of Sleep Deprivation on Gene Regulation

> **NIH NIH R01** · UNIVERSITY OF IOWA · 2020 · $385,990

## Abstract

Project Summary/Abstract
Alzheimer's Disease is one of the leading causes of death in the United States. With increases in longevity
over the past fifty years, the numbers of individuals living longer and being affected by Alzheimer's Disease is
expected to increase significantly over the next decade, imposing tremendous health care and economic
burdens on individuals, families and society. Historically, sleep disorders and sleep disturbances have been
viewed as symptoms of Alzheimer's Disease and other neurodegenerative diseases; however, recent research
has implicated sleep deprivation or sleep disturbances as contributing factors to Alzheimer's Disease
vulnerability and as a meaningful factor in the rate of disease progression and pathogenesis. In addition to
contributing to the decline in memory and cognitive function, sleep deprivation has also been shown to
increase tau pathologies and amyloid beta peptides, pathological hallmarks of Alzheimer's Disease. Given the
dramatic rise in sleep deprivation across adults, teenagers and children over the past twenty years, it is
imperative that we identify the mechanisms through which sleep deprivation affects Alzheimer's pathogenesis.
The hippocampus, a critical brain region for memory, is particularly susceptible to the effects of acute sleep
deprivation and is one of the first regions to exhibit phenotypic pathologies in Alzheimer's Disease. We
hypothesize that sleep deprivation affects targets RNA splicing and processing, and the available pool of
mRNA for translation to affect gene expression in tau pathogenesis. The objective of this Alzheimer's
Disease Supplement proposal is to identify the impact of sleep deprivation on cell-type specific gene
regulation and explicitly detail the pool of mRNA available for translation in a mouse model of
tauopathy related to Alzheimer's disease before and after tau pathologies occur. We will use an
advanced viral RiboTag strategy to specifically target excitatory neurons in the hippocampus followed by deep
RNA sequencing of total RNA and the mRNA associated with translating polyribosomes. The results from our
two stage experiments defining genome-wide interactions between sleep deprivation before the onset of tau
pathologies and after development of tauopathies with cell-type specific resolution on RNA fate and protein
synthesis, and the identification of cell-specific signatures of sleep deprivation, will provide significant insights
into the negative impacts of sleep deprivation on tau pathogenesis related to Alzheimer's Disease, potentially
leading to the development of novel therapeutics to counteract the consequences of sleep loss on cognition
and neurodegenerative disorders.

## Key facts

- **NIH application ID:** 10123651
- **Project number:** 3R01AG062398-02S1
- **Recipient organization:** UNIVERSITY OF IOWA
- **Principal Investigator:** EDWIN TED G. ABEL
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $385,990
- **Award type:** 3
- **Project period:** 2019-08-01 → 2024-04-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10123651

## Citation

> US National Institutes of Health, RePORTER application 10123651, Mechanistic Studies on the Impact of Sleep Deprivation on Gene Regulation (3R01AG062398-02S1). Retrieved via AI Analytics 2026-05-27 from https://api.ai-analytics.org/grant/nih/10123651. Licensed CC0.

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