title: A hypnic hypothesis of Alzheimer's disease.
abstract: BACKGROUND
  Understanding the pathophysiology of Alzheimer's disease (AD) is of fundamental importance for improved diagnosis, monitoring and ultimately, treatment.
  
  
  OBJECTIVE
  A role for the sleep-wake cycle in the pathogenesis of AD has been proposed, but remains to be worked out in detail.
  
  
  METHODS
  Here we draw together several lines of previous work to outline a 'hypnic hypothesis' of AD.
  
  
  RESULTS
  We propose that altered function of brainstem neurotransmitter pathways associated with sleep, promotes regionally specific disintegration of a cortico-subcortical 'default mode' brain network that is selectively vulnerable in AD.
  
  
  CONCLUSIONS
  The formation of a dynamic toxic state within this vulnerable network linked to sleep-wake disruption, would in turn lead to failure of synaptic repair, increased transmission of pathogenic misfolded proteins and a self-amplifying neurodegenerative process. We consider the evidence for this hypnic hypothesis and the implications that follow on from it.
authors: Dementia Research Centre, UCL Institute of Neurology, University College London, London, UK.
authors: Camilla N
authors: CN
authors: Clark
authors: Jason D
authors: JD
authors: Warren
mesh_terms: D000544:Alzheimer Disease / Q000150:complications* / Q000473:pathology*; D001933:Brain Stem / Q000378:metabolism* / Q000473:pathology / Q000503:physiopathology; D006801:Humans; D009434:Neural Pathways / Q000378:metabolism / Q000503:physiopathology; D020178:Sleep Disorders, Circadian Rhythm / Q000209:etiology*; D009435:Synaptic Transmission
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