Sleep deprivation has become a badge of honor in our modern society. Competitions break out in coffee shop lines over who is functioning on the least number of Zzzzzs and living the most fast-paced life. Bragging rights come with ordering the eye-opener with a triple shot of espresso. Close our eyes and we risk missing a culturally shocking tweet or a groundbreaking news update. We know that not getting enough sleep can impair our memory, make us a hazard at the wheel, and contribute to anxiety, but according to recent research, sleep impairments may also contribute to amyloid plaque build-up in the brain and our risk for dementia and Alzheimer’s disease.
In a recent publication in Science Translational Medicine, the Holtzman laboratory at Washington University in St. Louis set out to examine why the amount and quality of sleep declines in Alzheimer’s patients. The first piece of evidence the researchers had was from reports that Alzheimer’s brains have accumulations of amyloid-β plaques in regions of the brain critical for memory, including the hippocampus. These aggregations begin to form approximately 10 to 15 years before memory impairments occur. In this “pre-clinical” Alzheimer’s phase, neural networks have impaired connections in regions affected by amyloid deposits.
Using a mouse model for Alzheimer’s disease, the team found that the formation of plaques was accompanied by deterioration in the sleep-wake cycle. The team took advantage of the ability of Aβ to be secreted by neurons into the interstitial fluid (ISF). ISF is the solution in the extracellular space that bathes cells. In normal mice (called wild-type) or young mice with Alzheimer’s mutations that do not have plaques, Aβ levels increase in the ISF during wakefulness and decrease during sleep (Roh et al., 2012). The big question on the researchers’ minds was how do these changes in Aβ metabolism contribute to deteriorations in sleep.
Interestingly, in both young adult humans with mutations for Alzheimer’s disease and older mice with genetic mutations leading to the build-up of Aβ plaques, it was discovered that Aβ levels in the ISF stopped fluctuating; eliminating the Aβ plaques in mice through an immunization for Aβ42 normalized the sleep-wake cycle and restored the fluctuations in Aβ in the ISF. These data suggest that sleep-wake behavior and fluctuations in Aβ may be a preceding event to Alzheimer’s disease and a biomarker to give clinicians a clue as to which individuals may be at risk for developing the disease. So the next time you find yourself staring at the clock past 3:00 AM, leave the party early with the excuse that disrupted sleep has the potential to lead to Aβ aggregation, and do your sleep-wake cycle a favor!
Roh J.H., Huang Y., Bero A.W., Kasten T., Stewart F.R., Bateman R.J. & Holtzman D.M. (2012). Disruption of the Sleep-Wake Cycle and Diurnal Fluctuation of -Amyloid in Mice with Alzheimer’s Disease Pathology, Science Translational Medicine, 4 (150) 150ra122-150ra122. DOI:10.1126/scitranslmed.3004291
Images via Saito T., Suemoto T., Brouwers N., Sleegers K., Funamoto S., Mihira N., Matsuba Y., Yamada K., Nilsson P., Takano J. & Nishimura M. (2011). Potent amyloidogenicity and pathogenicity of Aβ43,Nature Neuroscience, 14 (8) 1023-1032. DOI: 10.1038/nn.2858 and made by Jooyeun Lee.
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