Lost sleep could set you up for Alzheimer’s

In two new studies, researchers found that lack of sleep could help promote the development of Alzheimer’s disease.

The first study shows that different forms of a key Alzheimer’s protein known as tau arise in a predictable sequence as the disease develops, starting more than 20 years before symptoms appear.

The second study shows that lack of sleep increases levels of a particular form of tau that is harmful.

Alzheimer’s disease is the most common form of dementia, affecting more than 5 million people in the US, but doctors have limited advice on how to protect against it.

The disease develops silently in the brain for two decades or more before people begin showing the characteristic signs of forgetfulness and confusion.

Understanding that the silent phase could be key to preventing this devastating condition.

The new findings help explain why poor sleep is linked to an increased risk of Alzheimer’s dementia and could lead to ways to identify where people stand on the road to Alzheimer’s.

Alzheimer’s disease is linked to two main proteins: amyloid and tau. Both are normal brain proteins that become harmful when they collect into clumps.

Amyloid plaques first appear two decades or more before cognitive symptoms arise. Tau tangles form later, just as the damage becomes visible on brain scans and cognitive skills begin to decline.

The team suspected that tau might start undergoing changes very early in the disease process that eventually results in the formation of tangles—and cognitive decline.

To find out, they studied people enrolled in the Dominantly Inherited Alzheimer Network (DIAN).

Such participants have rare genetic mutations that cause them to develop Alzheimer’s at young ages, around the same ages their parents developed the disease.

While devastating for families, these mutations allow researchers to know who will develop the disease and when.

The researchers analyzed samples of cerebrospinal fluid—the fluid that surrounds the brain and spinal cord—from 370 DIAN participants.

They were looking for tau that had been chemically modified by the addition of a phosphate group, a process known as phosphorylation.

They detected phosphorylated forms of tau in some of the earliest samples—around the same time amyloid plaques appear and long before tau tangles arise.

Further, the forms of phosphorylated tau arose in a specific sequence.

The researchers found that one form—phosphorylated tau-217—arose 21 years before the expected age of symptom onset and stayed high until just before signs of cognitive decline became detectable.

Other phosphorylated forms appeared later. Altogether, their data outlined a clear sequence of tau changes in the years leading up to Alzheimer’s dementia.

The team says by looking at tau phosphorylation, scientists can pinpoint where people are in the disease.

If everything is normal except for one of these, then people have a long way to go before you develop symptoms. But if a lot are abnormal, they are within a few years of developing symptoms.

One author of the two studies is Randall J. Bateman, professor of neurology.

The studies appear in Nature Medicine and Annals of Neurology.

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