Alzheimer’s kills neurons that keep us awake

US scientists have discovered why excessive napping is recognised as an early warning sign for Alzheimer’s.

A new study from the University of California, San Francisco, shows that the disease directly attacks brain regions responsible for wakefulness during the day, making them among the first casualties of the process of neurodegeneration.

The research also suggests that a protein known as tau contributes more directly to this degeneration than the more extensively studied 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,” says senior author Lea Grinberg.

The findings are published in the journal Alzheimer’s and Dementia. 

Grinberg and colleagues measured Alzheimer’s pathology, tau protein levels and neuron numbers in three brain regions involved in promoting wakefulness from 13 deceased Alzheimer’s patients and seven healthy control subjects.

They found that Alzheimer’s patients had significant tau build-up in all three regions, which had lost as much 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,” says lead author Jun Oh. 

“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.”

In contrast, there was no such impact on the neurons of seven patients with other forms of neurodegenerative dementia – progressive supranuclear palsy (PSP) and corticobasal disease (CBD) – despite comparable levels of tau build-up.

“It seems that the wakefulness-promoting network is particularly vulnerable in Alzheimer’s disease,” Oh says. 

The results are in line with the group’s earlier study that showed that people who die with elevated levels of tau protein in their brainstem – corresponding to the earliest stages of Alzheimer’s disease –  have already begun to experience changes in mood, such as anxiety and depression, as well as increased sleep disturbances.

“Our new evidence for tau-linked degeneration of the brain’s wakefulness centres provides a compelling neurobiological explanation for those findings,” Grinberg says. 

“It suggests we need to be much more focused on understanding the early stages of tau accumulation in these brain areas in our ongoing search for Alzheimer’s treatments.”