If you often have trouble sleeping, will Alzheimer's disease come to you?

If you often have trouble sleeping, will Alzheimer's disease come to you?

Author: Tian Dawei, popular science creator

Reviewer: Li Jingjing, Professor and Chief Physician, Department of Neurology, Beijing Tiantan Hospital

Lack of sleep is too common for modern people. Writing papers, watching TV series and staying up late are commonplace, and all kinds of worries can also make us toss and turn and have a bad sleep all night.

But staying up late also brings us obvious troubles. The next day, we feel groggy and can't concentrate. And we forget what others just reminded us of in a blink of an eye.

A recent study also found that long-term lack of sleep may also lead to the deposition of beta-amyloid protein in the brain[1]. Beta-amyloid protein is the main component of amyloid plaques in the brains of patients with Alzheimer's disease. Its increased deposition may mean an increased risk of developing Alzheimer's disease (commonly known as senile dementia).

Dyed amyloid beta protein (brown), image source: wikimedia

So how does lack of sleep affect our brains? Does staying up late often really make us suffer from Alzheimer's disease at a young age? To figure this out, let's start with the brain in sleep.

What does the brain do while we dream?

The importance of sleep to the body is self-evident, but we may have some misunderstandings about sleep.

Some people think that when we lie in bed and fall asleep, our brain begins to rest. But in fact, after we fall asleep, our brain does not completely shut down, it still has many important things to do.

1. Consolidate memory and regulate emotions

During sleep, especially during the rapid eye movement stage (the stage of sleep when dreams occur), the brain consolidates new information collected during the day, so sleep is very important for forming long-term memories.

A sleep cycle, red is rapid eye movement sleep (REM), image source: wikimedia

In addition to consolidating memory, during the REM phase, the brain also processes information related to emotions, reducing the impact of negative emotions on us, which is also crucial for us to maintain a good mental state. Therefore, many people become more unstable in temper after staying up late.

2. Repair damaged neuron cells

In addition to consolidating memories and regulating emotions, sleep is also crucial for repairing neurons.

It should be noted that this does not mean that neurons can only be repaired in a sleep state, but a 2019 study found that sleep can affect chromosome dynamics, thereby better promoting neuronal cells to repair damaged DNA[2].

3. Remove harmful metabolites

During sleep, the brain also clears out some metabolites, including beta-amyloid protein, alpha-synuclein, and abnormal tau protein, which are proteins associated with neurodegenerative diseases.

Abnormal Tau protein Image source: wikimedia

There are several ways for the brain to eliminate harmful metabolites, one of which is through the glymphatic system. The working method of this system can be simply understood as: through the flow of cerebrospinal fluid, harmful metabolites are flushed out from around neuronal cells and taken to other organs for decomposition.

Researchers have found that this system works more efficiently during sleep. For example, a study published in Science in 2013 showed that during natural sleep or anesthesia, the gap between cells increases by 60%, which helps to increase the clearance rate of amyloid-β (the clearance rate of amyloid-β during sleep is about twice that of wakefulness) [3].

Image source: Clearance rates of amyloid-β in the awake, sleeping, and anesthetized groups. Image source: From reference 3.

Lack of sleep and Alzheimer's disease

Since the brain does so many important things during sleep, chronic sleep deprivation can cause serious changes in the brain.

For example, in May 2023, an article published in Science Translational Medicine, a subsidiary of Science, pointed out that long-term lack of sleep may increase the risk of Alzheimer's disease [1].

The researchers used a sleep deprivation device to interfere with the experimental mice, keeping them in a state of long-term sleep deprivation (about 6 weeks). Afterwards, they studied the brains of these mice. The researchers found that compared with the control group, the mice in a long-term sleep deprivation state had beta-amyloid deposits in their brains, which means that these mice may have an increased risk of developing Alzheimer's disease.

Scientists speculate that this situation may be related to two factors.

First of all, when in a state of long-term wakefulness, neurons in the brain will remain active for longer periods of time, and increased neuronal activity will itself lead to the release of beta-amyloid protein, increasing the production of these "poisons" from the source.

But more importantly, something called microglia affects the removal of these "poisons."

Microglia (green) and neurons (red), Image source: wikimedia

Microglia are immune-related cells in the nervous system. Under normal circumstances, microglia play a role similar to that of sentinels in the brain, patrolling the brain to detect damaged cells or signs of disease. Once they detect something, they become activated and help repair damaged tissue.

However, long-term sleep deprivation affects the normal function of microglia, causing them to become over-activated, affecting the clearance of amyloid-β plaques by immune cells, leading to amyloid-β deposition.

Lack of sleep can also cause problems

I have previously discussed the effects of long-term lack of sleep on the brain, but is it okay to stay up all night once or twice? Not really.

A human study in 2018 found that staying up late once was enough to cause the accumulation of beta-amyloid protein in the subjects’ brains. The study also found that the effects of sleep deprivation (staying up late) on the brain were unrelated to genetic risk. In other words, even if there is no risk of Alzheimer’s disease in your family, staying up late may still affect the accumulation of beta-amyloid protein [4].

Of course, in this study, the researchers did not delve into whether the accumulation of beta-amyloid caused by staying up late once can be restored after rest. But occasionally staying up late may still bring other dangers.

The most typical example is that after staying up late, even if you don’t drink, you may still “drive under the influence”.

If you have ever stayed up late, you must be familiar with the condition called "brain fog", which feels hazy as if there is a layer of fog separating you from the world.

An article published in Nature Medicine in 2017 analyzed the reasons behind "brain fog". After staying up late, the activity of brain neurons will be slower and weaker than usual. This will make you lose focus and react more slowly, just like being drunk [5].

If driving under the influence is dangerous, then driving or riding a bike in this brain foggy state is equally dangerous. So if you pull an all-nighter, try not to drive the next day if you can.

Since staying up late has such a big impact on the brain, do you still plan to stay up late today?

References:

[1]Parhizkar S, Gent G, Chen Y, et al. Sleep deprivation exacerbates microglial reactivity and Aβ deposition in a TREM2-dependent manner in mice[J]. Science translational medicine, 2023, 15(693): eade6285.

[2]Zada D, Bronshtein I, Lerer-Goldshtein T, et al. Sleep increases chromosome dynamics to enable reduction of accumulating DNA damage in single neurons[J]. Nature communications, 2019, 10(1): 895.

[3]Xie L, Kang H, Xu Q, et al. Sleep drives metabolite clearance from the adult brain[J]. science, 2013, 342(6156): 373-377.

[4]Shokri-Kojori E, Wang GJ, Wiers CE, et al. β-Amyloid accumulation in the human brain after one night of sleep deprivation[J]. Proceedings of the National Academy of Sciences, 2018, 115(17): 4483-4488.

[5]Nir Y, Andrillon T, Marmelshtein A, et al. Selective neuronal lapses precede human cognitive lapses following sleep deprivation[J]. Nature medicine, 2017, 23(12): 1474-1480.