Extreme daytime sleepiness is often a top symptom of Alzheimer's disease but what, exactly, causes it? New research finally brings us an answer.
Many people with Alzheimer's disease have a tendency to sleep a lot during the day, even when they have had a full night's sleep.
Based on links between excessive sleepiness and neurodegenerative conditions, researchers are speculating that looking at daytime napping patterns could help predict the development of Alzheimer's.
But what remains unclear is why, exactly, people with this condition experience the need to sleep so often.
A new study, conducted by researchers at the University of California, San Francisco (UCSF) and other institutions, shows that people with Alzheimer's disease experience major brain cell loss in regions of the brain tasked with keeping us awake.
The findings, which appear in the journal Alzheimer's & Dementia, also suggest that an overaccumulation of tau protein triggers these brain changes.
In Alzheimer's disease, tau proteins form tangles that disrupt communication between neurons (brain cells) and impact cell health.
"Our work shows definitive evidence that the brain areas promoting wakefulness degenerate due to accumulation of tau — not amyloid protein [another protein that can become toxic in Alzheimer's disease] — from the very earliest stages of the disease," explains senior author Dr. Lea Grinberg.
Tau: 'a direct driver of cognitive decline'?
In the study, Dr. Grinberg and the team analyzed the brains of 13 deceased people who had Alzheimer's disease, as well as those of seven deceased individuals who had not experienced clinical neurodegeneration. The researchers obtained these samples from UCSF's Neurodegenerative Disease Brain Bank.
The team found that, in comparison with healthy brains, those affected by Alzheimer's disease had a high level of tau across three regions that are key to staying awake, namely the locus coeruleus, the lateral hypothalamic area, and the tuberomammillary nucleus. Not only this, but these regions had actually lost 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," notes the study's 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," Oh explains.
For further clarification, the researchers went on to conduct a postmortem analysis of brain samples from seven people who had progressive supranuclear palsy and corticobasal disease. These are two forms of dementia that are characterized specifically by the overaccumulation of tau protein.
In these samples, the scientists did not find the same loss of neurons in areas connected with states of wakefulness, which suggests that this destructive loss may only occur in Alzheimer's disease.
"It seems that the wakefulness-promoting network is particularly vulnerable in Alzheimer's disease. Understanding why this is the case is something we need to follow up in future research," says Oh.
Previous evidence uncovered by Dr. Grinberg and colleagues also suggests that tau protein may have a direct impact on brain degeneration in Alzheimer's disease. In that study, the team found that people who died with high levels of tau in their brain stem — which corresponds to early stage Alzheimer's disease — had begun to develop mood changes and sleep problems.
"Our new evidence for tau-linked degeneration of the brain's wakefulness centers provides a compelling neurobiological explanation for those findings," says Dr. Grinberg.
"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," she adds.
"This research adds to a growing body of work showing that tau burden is likely a direct driver of cognitive decline."
Dr. Lea Grinberg