Sleep quality and amount are known to decline with age and to a greater extent in Alzheimer disease patients. Using the APPswe/PS1δE9 mouse model of Alzheimer’s disease the authors of this study found that amyloid beta (Aβ) aggregation appears to disrupt the sleep-wake cycle and diurnal fluctuation of Aβ.
Aggregation of Aβ in the brain is known to occur years before the clinical onset of Alzheimer’s disease. Before Aβ aggregation, concentrations of extracellular soluble Aβ in the interstitial fluid of the brain correlate with the amount of Aβ deposition seen later in the brain.
In this study, a normal sleep-wake cycle was seen in the APPswe/PS1δE9 mice before Aβ plaque formation. However, after amyloid plaque formation the sleep-wake cycle markedly deteriorated and diurnal fluctuation of Aβ in the interstitial fluid was disrupted. This parallels data on cerebrospinal fluid Aβ in human subjects with presenilin mutations, where cerebrospinal fluid Aβ is also markedly attenuated after Aβ plaque formation and shows a disruption of diurnal fluctuation. Virtual elimination of Aβ deposits in the mouse brain by active immunization with Aβ(42) normalized the sleep-wake cycle and the diurnal fluctuation of Aβ in the interstitial fluid.
This study provides useful data suggesting a link between sleep disruption and brain amyloid beta aggregation in the brains of Alzheimer’s disease subjects.
Roh JH, Huang Y, Bero AW, Kasten T, Stewart FR, Bateman RJ, Holtzman DM: Disruption of the Sleep-Wake Cycle and Diurnal Fluctuation of β-Amyloid in Mice with Alzheimer’s Disease Pathology. Science Transl. Med. 4(150):150ra122 (2012).
http://www.ncbi.nlm.nih.gov/pubmed/22956200
See also:
Disrupted sleep may predict Alzheimer’s
Poor sleep patterns linked to formation of Alzheimer’s plaques.
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