Alzheimer's Destroys Neurons That Keep Us Awake, Finds New Study

Alzheimer's is a debilitating disorder that comes with many problems one of which is that people with the disease tend to nap excessively during the day. In the past, this was often attributed to the fact that the disease causes sleep-related issues at night.

Directly attacking the brain regions responsible for wakefulness

However, now UC San Francisco scientists may have discovered that Alzheimer's disease directly attacks the brain regions responsible for wakefulness. New research is demonstrating that these regions are among the first to be impacted by neurodegeneration.

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As such, the researchers argue that excessive daytime napping could even serve as an early warning sign of the disease. Furthermore, the novel research found a connection between the damage caused by Alzheimer's and a protein known as tau.

This is important because up to now that damage was attributed to the amyloid protein. "Our work shows definitive evidence that the brain areas promoting wakefulness degenerate due to accumulation of tau -- not amyloid protein -- from the very earliest stages of the disease," said study senior author Lea T. Grinberg, MD, PhD, an associate professor of neurology and pathology at the UCSF Memory and Aging Center and a member of the Global Brain Health Institute and UCSF Weill Institute for Neurosciences.

For their study, the researchers measured tau protein levels and neuron numbers in three brain centers involved in keeping us awake from 13 deceased Alzheimer's patients and seven healthy control subjects. What they found was that the brains of Alzheimer's patients had significant tau buildup in all three wakefulness-related brain areas and had lost as many as 75% of their neurons.

"It's remarkable because it's not just a single brain nucleus that's degenerating, but the whole wakefulness-promoting network," said lead author Jun Oh, a Grinberg lab research associate. "Crucially this means that the brain has no way to compensate because all of these functionally related cell types are being destroyed at the same time."

A new focus on the Tau protein

The work may help to explain why the more widely studied amyloid protein has so far failed to produce effective Alzheimer's therapies. The researchers are arguing that the focus should be put on the tau protein.

"This research adds to a growing body of work showing that tau burden is likely a direct driver of cognitive decline," Grinberg said.

Tau focused treatments are currently in development at UCSF's Memory and Aging Center. The researchers believe they have the potential to improve sleep and Alzheimer's-related symptom. Better yet, they could slow the progress of the disease overall.

The new study was published August 12, 2019 in Alzheimer's and Dementia.