Sleep, the Brain, and Alzheimer’s

Sleep has always presented a problem for science. It is an activity in which we humans spend approximately one-third of our lives. So there must be some justification, but what is it? Dreaming is an important area of study. The healthymemory blog has a substantial number of posts on dreaming, which will not be reviewed here (to find them, enter “dreaming” into the search block of the healthymemory blog). Recent research has identified how waste materials are removed from the brain, and how this removal increases when we sleep. A healthymemory blog reader has led me to some of this research and I do thank him for his assistance.

For most of the body there is a complex system of lymphatic vessels that cleanse tissues of potentially harmful metabolic waste products, accumulations of soluble proteins and excess interstitial fluid. Unfortunately, the central nervous system lacks a lymphatic vasculature, so the problem was to identify how waste products are removed from the brain. Research by Maiken Nedergaard and her research group at the University of Rochester has appeared to have solved this problem.1 This finding is especially important as the breakdown of the brain’s innate clearance system might underlie the pathogenesis of neurodegenerative disorders such as Alzheimer’s, Parkinson’s, and Huntington’s disease, as well as ALS and chronic traumatic encephalopathy.

The research team injected fluorescent tracers into the brains of living mice, and then imaged the movement of the tracers using two-photon microscopy in real time. They were able to identify a complete anatomical pathway, which they dubbed the “glymphatic system” due to its dependence on glial cells performing a “lymphatic” cleansing of the brain interstitial fluid. (enter “glial” into the healthymemory blog search block to learn more about glial cells).

“During sleep, the cerbrospinal fluid flushed through the brain very quickly and broadly,” said Rochester neuropharmacologist Lulu Xi/”2. Another experiment revealed that sleep causes the space between cells to increase by 60%, allowing the flow to increase. When the mouse was awakened, the flow in the brain was greatly constrained.

“Brain cells shrink when we sleep, allowing fluid to enter and flush out the brain,” Nedergaard said. “It’s like opening and closing a faucet.”3 The research also found that beta-amyloid protein cleans out of the brain twice as fast in a sleeping rodent as in one who is awake.

This research once again underscores the importance of getting enough sleep. It also suggests that failures in this cleansing system might contribute to neurodegenerative disorders such as Alzheimer’s, Parkinson’s, and Huntington’s disease, as well as ALS and chronic traumatic encephalopathy. So this research opens up new research avenues for studying and, possibly curing or remediating these diseases.

2Kim, M. (2013). During sleep, the brain clears up. The Washington Post, October 20, p. A5.



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