Possible role of orexin and sleep changes in the development of Alzheimer's disease

Knockout of the orexin gene in APP/PS1 transgenic mice led to a marked decrease in Aβ pathology and an increase in sleep time.

• Age-related aggregation of amyloid-β is associated with disrupted sleep-wake cycles.
• In humans with preclinical Alzheimer's disease, poor sleep quality and reduced sleep duration have been noted.
• Loss of orexin-producing neurons is linked to narcolepsy and affects wakefulness.
• Focal overexpression of orexin in the hippocampus did not change total sleep/wakefulness or Aβ pathology.
• Increased wakefulness through orexinergic neuron rescue in orexin-deficient APP/PS1 mice resulted in heightened Aβ pathology.
• Modulation of orexin and its impact on sleep may influence amyloid-β pathology in the brain.

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