Natural Age-Related Slow-Wave Sleep Alterations Onset Prematurely in the Tg2576 Mouse Model of Alzheimer's Disease.

INTRODUCTION: Sleep insufficiency or decreased quality have been associated with Alzheimer's disease (AD) already in its preclinical stages. Whether such traits are also present in rodent models of the disease has been poorly addressed, somewhat disabling the preclinical exploration of sleep-based therapeutic interventions for AD. METHODS: We investigated age-dependent sleep-wake phenotype of a widely used mouse model of AD, the Tg2576 line. We implanted electroencephalography/electromyography headpieces into 6-month-old (plaque-free, n = 10) and 11-month-old (moderate plaque-burdened, n = 10) Tg2576 mice and age-matched wild-type (WT, 6 months old n = 10, 11 months old n = 10) mice and recorded vigilance states for 24 h. RESULTS: Tg2576 mice exhibited significantly increased wakefulness and decreased non-rapid eye movement sleep over a 24-h period compared to WT mice at 6 but not at 11 months of age. Concomitantly, power in the delta frequency was decreased in 6-month old Tg2576 mice in comparison to age-matched WT controls, rendering a reduced slow-wave energy phenotype in the young mutants. Lack of genotype-related differences over 24 h in the overall sleep-wake phenotype at 11 months of age appears to be the result of changes in sleep-wake characteristics accompanying the healthy aging of WT mice. CONCLUSION: Therefore, our results indicate that at the plaque-free disease stage, diminished sleep quality is present in Tg2576 mice which resembles aged healthy controls, suggesting an early-onset of sleep-wake deterioration in murine AD. Whether such disturbances in the natural patterns of sleep could in turn worsen disease progression warrants further exploration.

Rapid and reversible control of human metabolism by individual sleep states.

Sleep is crucial to restore body functions and metabolism across nearly all tissues and cells, and sleep restriction is linked to various metabolic dysfunctions in humans. Using exhaled breath analysis by secondary electrospray ionization high-resolution mass spectrometry, we measured the human exhaled metabolome at 10-s resolution across a night of sleep in combination with conventional polysomnography. Our subsequent analysis of almost 2,000 metabolite features demonstrates rapid, reversible control of major metabolic pathways by the individual vigilance states. Within this framework, whereas a switch to wake reduces fatty acid oxidation, a switch to slow-wave sleep increases it, and the transition to rapid eye movement sleep results in elevation of tricarboxylic acid (TCA) cycle intermediates. Thus, in addition to daily regulation of metabolism, there exists a surprising and complex underlying orchestration across sleep and wake. Both likely play an important role in optimizing metabolic circuits for human performance and health.