Pro: Alzheimer's disease and circadian dysfunction: chicken or egg?

Alzheimer's disease (AD) is a neurodegenerative disease that accounts for most cases of dementia. Besides progressive cognitive decline, circadian dysfunction is a prominent feature of AD. Circadian disruption is traditionally regarded as a downstream symptom of AD, but recent evidence suggests that circadian dysregulation may act to exacerbate AD pathology. A reciprocal link among sleep, circadian rhythms, and amyloid deposition has long been suspected, and data from both human and animal studies support this hypothesis. The sleep-wake cycle regulates amyloid-beta (Aβ) levels in both mice and humans. Sleep deprivation increases Aβ levels in mice, and sleep apnea and insomnia may be related to AD in humans. Furthermore, melatonin, the principal hormonal output of the circadian system, is dysregulated in AD, and this may be important because melatonin is protective in cells exposed to toxic Aβ. Initial evidence supports a reciprocal link among sleep, circadian rhythmicity, and AD. More investigation is necessary to replicate these studies and determine the extent to which the circadian system contributes to the pathogenesis of AD.