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Neurodegener Dis. 2013;12(4):165-76. doi: 10.1159/000350060. Epub 2013 Apr 26.

A hypnic hypothesis of Alzheimer's disease.

Author information

1
Dementia Research Centre, UCL Institute of Neurology, University College London, London, UK.

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.

CONCLUSION:

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.

PMID:
23635607
PMCID:
PMC3884167
DOI:
10.1159/000350060
[Indexed for MEDLINE]
Free PMC Article
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