# Sleep Disruption and Alzheimer's Disease Pathology

> **NIH NIH RF1** · UNIVERSITY OF COLORADO · 2020 · $191,303

## Abstract

PROJECT SUMMARY
Alzheimer's disease (AD) is a disease of aging. AD is the most common form of dementia, afflicting more than
5 million Americans aged 65 and older. By 2050 it is estimated that more than 14 million Americans will suffer
this disease, and that its direct financial impact will exceed $1.1 trillion. AD is particularly burdensome because
it impairs memory; it worsens with time; and there is no cure. Sleep disruption in AD is highly prevalent, and
changes in sleep architecture and circadian rhythmicity that result in excessive daytime sleepiness and
nighttime insomnia are well documented. Less well known is the impact of sleep or circadian disruption on the
etiology of the disease. Sleep facilitates Aβ clearance from brain, and sleep disruption increases Aβ in
cerebrospinal fluid. Aβ pathology impairs core clock genes and exacerbates neuroinflammation. Collectively,
these data suggest that sleep and circadian disruption induce responses that feed forward and contribute to, or
exacerbate AD pathology and accelerate disease progression. However, to our knowledge definitive studies to
determine the extent to which sleep disruption per se contributes to AD pathology have not been conducted.
We will use mice expressing an inducible mutant amyloid precursor protein (APP) transgene to temporally
dissociate sleep disruption and mutant APP expression from subsequent Aβ deposition and AD-like pathology.
Specifically, we will: 1) determine how chronic sleep disruption of transgenic mice alters the course of
pathology induced by expression of mutant APP; 2) determine if sleep disruption accelerates AD onset; and 3)
target a key mediator of innate immune activation and determine effects on responses to sleep disruption
and/or mutant APP expression. Outcome measures for each aim include assessments of cognitive
performance; synaptic plasticity; differential gene expression; glial activation; cytokine production;
neuroinflammatory signaling; and proteinopathy. Our multidisciplinary research team has demonstrated
expertise and possesses all requisite skills to successfully complete the proposed project. Successful
completion of this project will have a sustained impact on the field because we will elucidate the extent to
which, and potential mechanisms by which, chronic sleep disruption alters the progression of AD-like
pathology.

## Key facts

- **NIH application ID:** 10158913
- **Project number:** 3RF1AG064465-01S1
- **Recipient organization:** UNIVERSITY OF COLORADO
- **Principal Investigator:** CHARLES A HOEFFER
- **Activity code:** RF1 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $191,303
- **Award type:** 3
- **Project period:** 2019-08-01 → 2024-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10158913

## Citation

> US National Institutes of Health, RePORTER application 10158913, Sleep Disruption and Alzheimer's Disease Pathology (3RF1AG064465-01S1). Retrieved via AI Analytics 2026-05-27 from https://api.ai-analytics.org/grant/nih/10158913. Licensed CC0.

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