Attention problems can manifest as memory problems

Alzheimer's: daytime sleepiness as a harbinger?

Drowsiness as a warning signal: Pronounced daytime sleepiness could be the sign of the onset of Alzheimer's disease. As a study suggests, regions in the brain that are important for wakefulness are attacked even in the early stages of dementia. Accumulations of malformed tau proteins lead to massive cell loss in these waking centers. The beta-amyloid plaques typical of Alzheimer's disease, on the other hand, do not seem to play a role in this context.

Long before the first memory problems manifest themselves in Alzheimer's patients, the onset of dementia can already manifest itself through unspecific symptoms. For example, many sufferers develop pronounced daytime sleepiness. You sleep unusually much during the day and unintentionally nod off a lot.

There are different theories as to why this is so: Some researchers assume that Alzheimer's disease disrupts brain regions that are important for sleep even in the early stages and that daytime sleepiness is a sign of the nightly sleep disorders it triggers. Others suggest a lack of sleep as a possible cause of the disease. Poor sleep, it is believed, could promote the development of neurodegenerative processes.

A look into the Alzheimer's brain

Another possible explanation is now provided by Jun Oh from the University of California in San Francisco and his colleagues: They have found evidence that Alzheimer's directly affects the areas in the brain that are responsible for wakefulness during the day - and thus triggers the noticeable sleepiness of those affected.

To find out more about the connection between daytime sleepiness and Alzheimer's, the scientists examined brain tissue from 13 deceased dementia patients and seven control persons. In doing so, they focused primarily on three regions of a network that promotes wakefulness and attention: the locus caeruleus, the lateral hypothalamus and the nucleus tuberomamillaris.

Guard centers attacked

The evaluations revealed that, unlike in healthy brains, large amounts of misfolded tau proteins had accumulated in the waking centers of the Alzheimer's patient's brain. Along with beta-amyloid plaques, these thread-like proteins are the second malformed protein type in the brain of those affected and are located within the neurons.

This finding was accompanied by a drastic loss of cells. Up to 75 percent of the neurons in the examined brain regions had died, as the researchers report. "Our results show that the brain areas responsible for alertness begin to degenerate in the early stages of the disease," reports Oh's colleague Lea Grinberg.

Entire network affected

According to the team, it is noteworthy that the entire wakefulness-promoting network seems to be affected by this process. "That also means: the brain has no way of compensating for the loss because all these functionally related areas and cell types are destroyed at the same time," explains Oh.

But is the degeneration of these brain regions really characteristic of Alzheimer's? To check this, the scientists examined brain samples from seven people affected by two other degenerative diseases of the brain that are also associated with clumped tau proteins: progressive supranuclear palsy (PSP) and corticobasal degeneration (CBD).

A possible early warning sign

The result: Although the same amount of malformed tau protein was deposited in the brain in these people as in the Alzheimer's patients, the neurons that are important for wakefulness were largely spared in them. "It seems that this network is particularly at risk in Alzheimer's," says Oh.

If this connection is confirmed, daytime sleepiness could act as an important early warning sign of the onset of Alzheimer's disease, as the doctor and his colleagues emphasize - especially if the sleepiness cannot be explained by nightly sleep problems.

Tau protein in focus again

In addition, the phenomenon that has now been observed brings the tau protein back into focus. “Our results suggest that we need to focus more on the early stages of tau accumulation if we are to find an effective therapy,” stresses Grinberg. In fact, other findings from Alzheimer's research also suggest that the tau proteins could be a more effective target for therapies than the beta-amyloid plaques, which were previously the main cause. (Alzheimer's and Dementia, 2019; doi: 10.1016 / j.jalz.2019.06.3916)

Source: University of California San Francisco

August 14, 2019

- Daniela Albat