# A model of sleep-deprived neuropathology to study resilience to Alzheimers Disease

> **NIH NIH R01** · UNIVERSITY OF WASHINGTON · 2020 · $388,750

## Abstract

ABSTRACT AD SUPPLEMENT. A model of sleep deprived neuropathology to study resilience to Alzheimer's
disease (PARENT R01 AG057381. Physical resilience is a predictor of healthy aging in mice)
Resilience to Alzheimer's disease (AD) is a well-known clinical and pathological observation, but the
mechanisms involved are not known. Adequate sleep is a potential factor in maintaining resilience to
neurodegenerative conditions such as AD. Sleep deprivation is a major health concern in developed countries
and is associated with increasing age. Sleep disturbances increase the risk of dementia and AD and there is
growing evidence that poor sleep leads to acceleration in the pathogenesis and progression of
neurodegenerative disorders. A logical question is whether the prevention of sleep deprivation-induced
neuropathology and cognitive impairment will enhance resilience to AD. We have developed an aging mouse
model of short-term sleep deprivation that results in neurodegenerative changes and cognitive impairment and
is prevented by a mitochondrial specific peptide. Therefore, this “youthful” background would be expected to be
more resistant (resilient) to development of AD induced neuropathology and dementia. The hypothesis of this
supplemental proposal is that prevention of sleep-deprived neuropathology will enhance resilience to the early
development of Alzheimer's disease. The specific aim is to investigate neuropathology and cognitive
impairment in aging, sleep-deprived mice challenged with AAV Aβ42/P301Ltau. Cohorts will be treated with
the mitochondrial specific peptide SS31 before and during sleep deprivation. All mice will be examined for
cognition, neuropathology and molecular pathology. Because SS31 prevents the neuropathology and cognitive
impairment induced by sleep deprivation, it is expected that SS31 will be able to prevent the development of
Aβ42/P301Ltau pathology.

## Key facts

- **NIH application ID:** 10114108
- **Project number:** 3R01AG057381-04S1
- **Recipient organization:** UNIVERSITY OF WASHINGTON
- **Principal Investigator:** Warren C LADIGES
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $388,750
- **Award type:** 3
- **Project period:** 2017-09-15 → 2022-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10114108

## Citation

> US National Institutes of Health, RePORTER application 10114108, A model of sleep-deprived neuropathology to study resilience to Alzheimers Disease (3R01AG057381-04S1). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10114108. Licensed CC0.

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