Disrupted Deep Sleep Linked To Alzheimer's With Buildup Of Amyloid Plaques, Memory Loss

A lack of non-rapid eye movement sleep may be connected to the beta-amyloid plaque buildup characteristic of Alzheimer's. Alyssa L. Miller, CC by 2.0

In patients with Alzheimer’s disease, fragments of a naturally occurring protein form a plaque in the brain and this builds up and destroys their memories. New research suggests poor sleep may work hand-in-hand with this toxic accumulation of beta-amyloid plaque. Lack of sleep, particularly non-rapid eye movement deep sleep, may enable the attack on the memories of Alzheimer's patients, say scientists at UC Berkeley.

For some years, scientists have attached great importance to the accumulation of beta-amyloid plaque in the brains of Alzheimer's patients. Though scientists agree on many points, some theories have been and continue to be debated: Is overproduction of beta-amyloid or removal of this plaque the key to Alzheimer’s? Would clearing the brain of plaque result in a reversal of disease? Despite the failure of various plaque-destroying drugs, some scientists refuse to reverse course, as David Grainger indicates in this Forbes article. Obviously, choosing the right theoretical road is tough work.

Sleep and Alzheimer's

To better understand beta-amyloid's connection to Alzheimer's, then, one team of scientists co-led by Dr. Matthew P. Walker, a professor of neuroscience and director of the Sleep and Neuroimaging Laboratory at UC Berkeley, approached the problem at a new angle:

Since beta-amyloid plaque also appears in the brains of some people reporting sleep disorders, might there be a three-way link between beta-amyloid, sleep, and Alzheimer’s?

Some evidence of possible connections already exist. One 2013 University of Rochester study, for instance, found brain cells in mice shrink during non-rapid-eye-movement (non-REM) sleep to make space for cerebrospinal fluids to wash out toxic metabolites, including beta-amyloid.

“Sleep is helping wash away toxic proteins at night, preventing them from building up and from potentially destroying brain cells,” Walker stated in a press release. Meanwhile, in previous work, Walker and his co-researchers found the brain waves generated during non-REM sleep play a role in transferring memories from the hippocampus to longer-term storage in the frontal cortex.

Might this past research be a piece of the puzzle somehow?

For their newest study, then, Walker and his colleagues looked at the relationship between the quantity of beta-amyloid in the brain’s medial frontal lobe and non-REM deep sleep. First, the research group used PET scans to measure possible accumulation of beta-amyloid in the brains of 26 participants between the ages of 65 and 81. Participants also were hooked up to an EEG machine to measure their brain waves while they slept. Additionally, the researchers examined participants’ brains with a functional MRI (both before and after sleep) to measure activity during a memory task.  

In particular, the researchers tracked activity in the hippocampus and the prefrontal cortex.

“The more you remember following a good night of sleep, the less you depend on the hippocampus and the more you use the cortex,” Walker said. “It’s the equivalent of retrieving files from the safe storage site of your computer's hard drive, rather than the temporary storage of a USB stick.”

After compiling data from the various scans and tests, the scientists created statistical models and analyzed the results. Beta-amyloid plaque in the medial prefrontal cortex correlated with deep sleep — specifically the more plaque, the less NREM slow wave sleep. Considering this link, the researchers speculate that beta-amyloid “may impair hippocampus-dependent memory in older adults through its impact on NREM slow wave activity,” noted the researchers in their published study.

The big positive is that sleep is a potentially modifiable factor, so there is a possibility that a “therapeutic sleep intervention may minimize the degree of cognitive decline associated with beta-amyloid pathology in old age,” the researchers wrote. Sleeping to prevent the buildup of toxic proteins sounds like the most wonderful of cures.

Source: Mander BA, Marks SM, Vogel JW, et a. Beta-amyloid disrupts human NREM slow waves and hippocampus-dependent memory consolidation. Nature Neuroscience. 2015.

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