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Is It Possible To Degrade Alzheimer’s Plaque With Sleep?

Chronic insomnia can be an invitation to alzheimer's disease. Because sleep cleans our brains!
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  • Burak Talha Akın Burak Talha Akın

⌛ Reading time: 8 minutes

Published Date: 10th February 2020 13:07 pm

📝 Writer: Burak Talha Akın ✅ Editor: Aysuda Ceylan

Alzheimer’s Disease is probably the most merciless disease within the neurodegenerative diseases. Like other disease it leads to death. But it also takes memories and experiences slowly and gradually.

The first description of Alzheimer’s Disease was made by Alois Alzheimer. In the light of the symptoms of a German patient named Auguste Deter, which he tried to treat towards the end of 1890, he attempted to identify the disease and officially added it to the literature in 1901.

However, the history of Alzheimer’s Disease is not so short of course. In Ancient Greek records, we can see that some patients showed demantia symptoms and these symptoms attributed to elderliness.

Before we talk about the effects of sleep onto disease, it should be useful to look at characteristic features of Alzheimer’s Disease first.

Symptoms

As usually, Alzheimer’s Disease is distinguished several stages like many of diseases.

Alzheimer’s Disease is usually associated with forgetfulness which is partly true. But patients do not forget everything at all. They generally remember their mothers, children, traumatic memories. However, they can remember the memories which not so important for them.

Causes and Pathophysiology

Neuroscientists have two basis hypothesis for Alzheimer’s Disease: Amyloid Beta (Aβ) and Tau Hypothesis.

What is Amyloid Hypothesis?

Amyloid Beta is a peptide and it have different isoforms. We can assume that people who investigated Alzheimer’s Disease just a little bit knows the “plaques”. That is the cause of formation of plaques after all.

We have talked about Amyloid Beta has more than one isoforms. In a healthy human’s brain, we can generally obtain Aβ40. But in the peoples brain with Alzheimer’s Disease, the formation of Aβ42 is accelerated by some causes that we are going to explain later. Molecules of Aβ42 are more sticky than Aβ40 and they stick each other and create bigger plaques. You can ask that question: “So how does this Amyloid Beta occur?”

There is a protein type on lipid membranes of our neuron cells called Amyloid Precursor Protein (APP). We do not know the function of it yet.

In a healthy human, APP is splitted off by α-secratase and γ-secretase. For activating protein and maintain its process. After this modification, some toxic and sticky molecules occur. These molecules are degraded by Proteosomes.

By contrast with normal situation, β-secretase and γ-secretase mainly take part in Alzheimer’s Disease. Not α-secratase. Neuroscientists do not know how this process occurs (again) but it is mostly assumed that it’s cause is genetic originated. One of the cut pieces is Aβ42, as you can imagine. Here are the events that break right here.

The broken Aβ42s accumulate quickly and begin to form those famous plaques. These plaques are insoluble in water and are toxic to the nervous system.

Of course, we can ask this question with a good reason: “What is the task of this Aβ? It should not be just a “throw-away molecule”” Of course it must have a task, but we do not know for sure. Its main task is thought to be activating kinase enzymes. Let’s also add that it shows protective properties against oxidative stress and helps transport cholesterol.

Whats Tau Hypothesis?

Tau is a protein in our neurons whose main task is to stabilize microtubules that hold the cell together. The development of the Tau hypothesis actually took place, not separately from the Amyloid hypothesis, but as a subordinate to it.

The consequences of the amyloid hypothesis cause a series of conduction disorders in synapses located between neurons. These disorders cause changes in the structure of Tau protein. Proteins become hyperphosphorylated. Due to these changes, microtubules can no longer hold the neuron together, causing it to disintegrate. Axons and dendrites are broken. As a result, a “tangle” remains from a neuron.

Alzheimer’s Pathophysiology

Genetic

There are four main genes involved in Alzheimer’s disease.

Presenilines form one of the elements of γ-secretase. While PSEN1 is located on chromosome 14; PSEN2 is located on chromosome 1.

Apoliprotein-E is required for the metabolism of lipoproteins with high triglyceride content. In addition, individuals with two E4 alleles are 10 to 30 times more likely to have Alzheimer’s disease. (4)

There is a remarkable situation here. The APOE2 gene prevents the formation of plaques that cause Alzheimer’s, while the APOE4 gene does the opposite. How ironic! (5)

I think Alzheimer’s disease has been adequately described. Now let’s come to the benefits of sleep…

Sleep and its Effect on Alzheimer’s

We know the importance of sleep at any age. Our mother shakes us in her arms ,sings a lullaby and leave ourselves to the warm welcome of sleep. We don’t have to go old days. We also know that a sweet nap after a nice meal. There are few things in the world that are as beautiful as sleeping under an aspen tree.

But since the subject we’re talking about is the brain, let’s look at what we can say about it. That’s enough for a nostalgia.

Sleep is a basic need for our brain. Imagine that terrible day you couldn’t sleep for hours. Okay, if you thought. No need to say much. Probably you have difficulty in the simplest movements, even the simplest thinking actions.

But it seems that the only benefit of sleep is not to protect our cognitive abilities. It also “cleans” our brain. Which is not a new information. But his relationship with Alzheimer’s is relatively new.

This is exactly what has been investigated in the article published in PNAS journal on December 14, 2017 titled “β-Amyloid accumulation in the human brain after one night of sleep deprivation” (2).

Research

In the study, which included 22 healthy participants, the goal was to compare the amount of Aβ accumulated after resting after a night of sleep and the Aβ accumulated in the brain.

To measure the amount of Aβ; a radiotracer called Florbetaben-14, which connects to Aβ and shines brightly in the PET scan. Then, a PET scan was applied both in the night where there was a lack of sleep and in the morning after a well rested night. The results confirm the researchers’ hypotheses.

It was observed that the concentration of Aβ in the brain increased in the night when you had a lack of sleep.

RW(Rested-Wakefulness)
SD(Sleep Deprivation)
FBB SUVr (Concentration Marker)

The fact that Aβ accumulation is in the right hippocampus region makes it easier to associate the condition with Alzheimer’s disease. In the graph on the right, you can see that the situation in almost all patients confirms the hypothesis. Except for the hippocampus; it is stated that accumulation is concentrated in the thalamus, bilateral putamen, parahippocampus and right precuneus regions.

We said that the most obvious symptom of Alzheimer’s disease is memory impairment and learning disability. The Hippocampus, Putamen, Parahippocampus and Precuneus regions are the main regions responsible for memory and learning. (6) (7) The relationship between Alzheimer’s and Talamus is about the processing of sensory information. (2)

In the research, the difference between the duration of sleep and the amount of accumulation was also examined. It is stated that accumulation decreases as sleep duration increases.

ORAD -> Possibility of accumulation based on APOE
SH -> Sleep Hours

Cleaning Mechanism

So how does sleep do this? Just like the lymphatic system in our body that is used by our immune cells like a highway, our brains have a unique system. (In summary, one way the brain can clear waste, including amyloid-beta, is the circulation of the cerebrospinal and interstitial fluids. The fluid flows through cavities in the brain, washes neurons, and eventually carries toxic substances from the brain to the liver). This is called the “glymphatic system“.

Glymphatic System purifies the brain from toxic substances by working at maximum efficiency especially during sleep.

Glymphatic System

This system in the vertebrates allows the Cerebrospinal Fluid to enter the brain quickly and deeply and diverts metabolic wastes in the tissue cavity into the veins. (3) molecules that are toxic to the brain are removed from the brain.

As a result, a regular and quality sleep; not only does it reduce our risk of getting alzheimer’s disease, it also makes many positive contributions to our overall health.

  • In addition, i want to raise awareness for a thing. There is a project called Folding@Home created by Stanford University. You can attribute your computer’s processor power for analyizing improper protein folds with a program. For the enthusiasts, https://foldingathome.org/

I dedicate this article to my grandfather Zeki Kocaman, who died in December 2018 due to Alzheimer’s disease.

Stay with science.