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Updated: Jan 10, 2026
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Optogenetic Manipulation of Neural Circuits During Monitoring Sleep/wakefulness States in Mice
Published on: June 19, 2019
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BACE1 regulates sleep-wake cycle through both enzymatic and non-enzymatic actions
Hannah Heininger1, Xiao Feng2,3, Alp Altunkaya4
1Institute of Physiology and Pathophysiology, Friedrich-Alexander-Universität Erlangen-Nürnberg, Erlangen, Germany.
EMBO Reports
|November 20, 2025
Summary
Beta-secretase BACE1 inhibitors for Alzheimer's disease may impair cognition by disrupting sleep. BACE1 knockout and variant mice show altered sleep patterns, suggesting a role in sleep regulation.
Area of Science:
- Neuroscience
- Molecular Biology
- Pharmacology
Background:
- Beta-secretase BACE1 is a therapeutic target for Alzheimer's disease (AD) due to its role in amyloid-beta peptide production.
- Clinical trials of BACE1 inhibitors were discontinued due to cognitive side effects.
Purpose of the Study:
- To investigate the potential role of BACE1 in sleep regulation and its non-enzymatic functions.
- To explore the link between BACE1 activity, cognitive impairment, and sleep disturbances.
Main Methods:
- Analysis of sleep patterns in BACE1 knockout (BACE1-KO) mice.
- Characterization of sleep in transgenic mice expressing a proteolysis-deficient BACE1 variant (BACE1-KI).
- Comparison of sleep parameters, including EEG power spectra and sleep spindles, between mutant and wild-type mice.
Main Results:
- Both BACE1-KI and BACE1-KO mice exhibited reduced sleep during the light phase.
- Altered transition rates between sleep and wake states were observed in both mutant lines.
- Changes in sleep spindles and gamma-range EEG power spectra were noted.
Conclusions:
- BACE1 plays a role in regulating sleep-wake cycles, potentially through non-enzymatic functions.
- Cognitive impairments observed with BACE1 inhibitors may be linked to disrupted sleep.
- Further research into BACE1's role in sleep is crucial for resuming clinical trials.
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