# The metabolic interplay of sleep and Alzheimer's disease

> **NIH NIH R01** · WAKE FOREST UNIVERSITY HEALTH SCIENCES · 2021 · $706,014

## Abstract

PROJECT SUMMARY/ABSTRACT
A bidirectional relationship exists between Alzheimer’s disease and sleep, where disrupted sleep increases
amyloid-beta (Aβ) and tau pathology and conversely, Aβ and tau aggregation disrupt sleep. The sleep/wake
cycle is a master regulator of metabolic and neuronal activity, where daily oscillations in activity are coupled to
the production and clearance of Aβ and tau. Although modulating neuronal activity alters both sleep/wake cycles
and Aβ/tau release, less is known about how fluctuations in glucose metabolism drive changes in sleep and
Alzheimer’s disease related pathology. Therefore, the goal of this proposal is to determine whether changes in
metabolic activity lead to changes in neuronal activity to disrupt sleep in Alzheimer’s disease and whether
metabolic dysfunction can serve as a novel therapeutic target to rescue sleep and Alzheimer’s pathology. Using
hippocampal biosensors coupled with EEG/EMG recordings, this proposal will investigate how glycemic
variability and peripheral glucose intolerance affect sleep and Alzheimer’s disease in rodent models of
Alzheimer’s related pathology. Moreover, we will establish whether normalizing peripheral glucose homeostasis
through treatment with the diabetic medication, metformin, is sufficient to preserve and restore sleep architecture
in the setting of Alzheimer’s disease.

## Key facts

- **NIH application ID:** 10221598
- **Project number:** 5R01AG068330-02
- **Recipient organization:** WAKE FOREST UNIVERSITY HEALTH SCIENCES
- **Principal Investigator:** Shannon L Macauley-Rambach
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $706,014
- **Award type:** 5
- **Project period:** 2020-08-01 → 2025-04-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10221598

## Citation

> US National Institutes of Health, RePORTER application 10221598, The metabolic interplay of sleep and Alzheimer's disease (5R01AG068330-02). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10221598. Licensed CC0.

---

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