# Mechanisms of sleep fragmentation in a mouse model of Alzheimer's disease

> **NIH NIH RF1** · STANFORD UNIVERSITY · 2023 · $1,902,500

## Abstract

Alzheimer’s Disease (AD) is one of the most devastating diseases in older adults, in which sleep disorders and
cognitive function impairments usually require institutional care. A bidirectional link between alterations in sleep
patterns and AD has been proposed by multiple authors. We have recently identified a new mechanism of
sleep fragmentation in aged animals that involves downregulation of voltage-dependent KCNQ potassium
channels in arousal-promoting hypocretin (Hcrt)-producing neurons. Aβ accumulation may also contribute to
sleep fragmentation since sleep architecture is disrupted in both amyloid precursor protein knockin (APP-KI)
and APP/PS1 animal models of AD, as well as human AD patients. These data strongly suggest a causal
involvement of sleep alterations, Aβ accumulation in the progression of AD.
Here propose to: i);monitor the activity of wake-promoting Hcrt and LC neurons in the context of AD and
determine whether Aβ changes their intrinsic properties in slice recordings; ii) determine whether Aβ affects
the activity of NREM and REM sleep-active neurons and their ability to maintain sleep archtecture; iii)
determine whether pharmacological or optogenetic sleep enhancement delays Aβ accumulation and improves
cognitive function in two mouse models of AD. The proposed pharmacological experiments targeting arousal
circuits have high translational potential to increase sleep quality in the elderly and slow disease progression in
AD patients.

## Key facts

- **NIH application ID:** 10662118
- **Project number:** 1RF1AG082202-01
- **Recipient organization:** STANFORD UNIVERSITY
- **Principal Investigator:** Luis De Lecea
- **Activity code:** RF1 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2023
- **Award amount:** $1,902,500
- **Award type:** 1
- **Project period:** 2023-04-15 → 2026-03-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10662118

## Citation

> US National Institutes of Health, RePORTER application 10662118, Mechanisms of sleep fragmentation in a mouse model of Alzheimer's disease (1RF1AG082202-01). Retrieved via AI Analytics 2026-05-27 from https://api.ai-analytics.org/grant/nih/10662118. Licensed CC0.

---

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