The aims of this project are to develop new technologies to identify and track sleep and wakeabnormalities present in mouse models of Alzheimer's disease (AD), as well as to test a sleep enhancementtechnology for applications in AD animal research. Signal Solutions, LLC, has previously developed andcommercialized a piezoelectric based system for noninvasive, high-throughput sleep and wake monitoring ofrodents. Automated scoring of sleep and wake allows for simultaneous recordings of many animals over longerperiods, with little burden on the researcher, rivalling EEG/EMG methods that are more complicated andexpensive to perform. Behavioral changes in sleep and wake can precede memory loss in the progression of Alzheimer'sdisease (AD). Clinical studies suggest sleep disturbances are exhibited in a high percentage of AD patients.Animal models of AD also display sleep disturbances and some models show changes in wake behaviorsbefore the molecular hallmarks and memory problems appear, as clearly occurs in human AD. In the treatmentof AD, a potential therapeutic target is preventing the aggregation of pathogenic forms of amyloid-beta (A-beta)and tau. Waste clearance in the brain has been shown to be increased with increased sleep, includingclearance of A-beta. Recently, non-pharmacological approaches using mechanical devices for rocking haveshown promise for sleep enhancement, which could be applied to AD research. The specific aims of this project are to 1) Develop advanced sleep/wake tracking technology: Add anew multipoint touch sensor to our current piezoelectric technology that together will identify specific behaviorsassociated with AD progression, tested with AD mouse model 3xTg. 2) Develop Sleep EnhancementTechnology: Modify our current MouseQwake sleep-disruption system for mechanical sleep-enhancement,with companion sleep and wake tracking capabilities.Anticipated Outcomes: The envisioned product is a home cage sensor and software that will allowresearchers to accurately measure changes in sleep and wake during long-term AD disease progression, aswell as track subtle changes in behavior in AD model mice. This system will minimize the amount of work, timetesting behaviors, and time for analyzing the videos or electrophysiology that is currently a major bottleneck.An expanded MouseQwake system will provide a tool for sleep manipulation of both sleep enhancement anddisruption as well as simultaneous sleep/wake and behavioral recording. If successful, a Phase II investigationwill involve large scale studies of multiple AD rodent models, and continue iterative improvements to bothhardware and software developed in phase I.
Public Health Relevance Statement: Sleep disruption is now recognized not only as an early symptom of Alzheimer's Disease (AD),
but also a contributor to its ongoing development, and thus sleep enhancement is a promising
approach to slow the disease. This proposal intends to provide new technology to facilitate
preclinical studies in AD model mice, including long term monitoring of behaviors associated
with disease progression, and a new method to manipulate and enhance sleep in mice to
assess effects on disease and interventions.
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