Potential role of orexin and sleep modulation in the pathogenesis of Alzheimer’s disease

Nov 26, 2014The Journal of experimental medicine

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

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Abstract

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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