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The latest news in Alzheimer’s research

Photo: Patients with Alzheimer’s often feel anxious and lost in their everyday lives (Image: Gerd Altmann/Pixabay).

My grandmother is 87 years old; she has Alzheimer’s disease. She can still remember her family but despite of some early memories, she doesn’t have much left of her life. My Oma has forgotten all about her breakfast by the time she leaves the kitchen. She does not know what she did today, or the day before. I cannot imagine what it must have felt like, when she first started to feel the decay of her own self.  Or what it feels like, now that the head is just filled with darkness. I do know that she is often sad, confused and sometimes scared, because she does not get along in life anymore. I wish, I could do something to help her, but to this date, there is no a cure.  

Alzheimer’s, a brain disease in which memory and the general ability to think deteriorate with age. Around 28 million people worldwide suffer from it currently, but due to the increased life expectancy, more are expected to be affected in the future. A diagnosis is often only possible in late stages, when the brain damage is already well advanced. That is why researchers are currently focusing their work both on early detection and on curing the disease, or at least on stopping its progression 1.

It often starts harmlessly: a misplaced key or forgotten appointment. At a certain age, forgetfulness is normal, but if more symptoms arise, it can mean that a person has dementia. Those affected are increasingly impaired in their ability to speak, think and solve problems (summarized as cognitive skills). But changes in motor skills, emotional balance and social behavior occur as well. Alzheimer’s is a form of dementia in which the damage to the brain is linked to processes that take place directly in the organ 1.

What happens in the brain of people who develop Alzheimer’s?
The cause of the disease are certain proteins that cease to function properly because of structural changes. In general, proteins consist of long chains. Each of these chains fold in a specific shape. The properties of proteins, and thus their functions, depend very much on the way they fold. Just like a sheet of paper can be used to fold a boat that floats on the water or an airplane that flies through the air. However, if you fold the page incorrectly, the plane crashes. And just like that, wrongly folded proteins can harm the brain.

This is what happens with tau proteins. Normally they have a useful function in the brain. They regulate the architecture of the flexible support tissue of individual brain cells. This organ is thus elastic and can remain malleable to a certain extent. But if tau proteins are not folded properly, they lose their function. Instead, they combine to form large structures that are deposited in the brain. These deposits are called filaments and scientists consider them as a cause of Alzheimer’s disease 2.

Image 1: Synapses of healthy people (left) and people with Alzheimer’s disease (right). The β-amyloid plaques form on the synapses, which waste away with time. The tau filaments, on the other hand, are deposited inside the neurons.

Furthermore, deposits of so-called β-amyloid peptides occur in brains of people suffering from Alzheimer’s. These are fragments of proteins that also form large structures and accumulate as so-called plaques. However, the influence of tau filaments on cognitive skills is considered greater, which is why research is now more focused on them 3.

Can a diagnosis be made before the brain is damaged?
Scientists are searching for minimally invasive methods with which the disease can be recognized very early, preferably before the brain has been damaged. It is possible to detect deposits of tau proteins in the brain using colorants. But the misfolded proteins can also be found outside the brain. As they are transported away via the blood-brain barrier. The proteins pass from the head into the brain-spinal cord fluid and can be detected there, in samples taken by a lumbar puncture. However, both methods are complex and expensive. Doctors only perform them when the patient’s cognitive abilities have already been impaired. But what if you could recognize the disease before the first problems are noticeable? This can be done with a blood test because the proteins are transported there from the brain-spinal cord fluid. And indeed, studies show that people with elevated blood tau levels have a 76 % chance to develop Alzheimer’s in the years that follow. A prophylactic test could be carried out at the family doctor from a certain age in order to quickly initiate countermeasures if necessary 4.

The scientists could furthermore show that increased tau values ​​correlate with other Alzheimer’s risk factors. These include cardiovascular diseases, gender and level of education. Women have a higher risk, just like less educated people. Subjects with greatly increased amounts of tau in their blood are even more likely to get sick than those with slightly elevated levels. But not all people with increased values ​​get Alzheimer’s. An initial blood finding could still be a reason for a brain scan, which in turn allows a very early diagnosis 4.

Image 2: The cross section shows how a healthy brain (left) looks compared to a sick brain (right). At the initial stage, tau filaments are stored in the hippocampus and the entorhinal cortex. From these areas, they eventually spread out in the brain. It is believed that the exacerbation of the disease can halted by fighting the tau deposits early and preventing their spreading. Both areas of the organ shrink due to the disease. The entorhinal cortex controls memory, ability to navigate and sense of time, while the hippocampus regulates the transition of memories from short-term to long-term memory. The fact that these areas are particularly affected, explains the forgetfulness and motor impairment of Alzheimer patients.

How lifestyle affects Alzheimer’s risk
Alzheimer’s has long been associated with lack of sleep. In order to assess the extent of the risk, researchers kept their test subjects awake for a whole night and measured tau values ​​in their blood. They compared them with values ​​from the same subjects after a restful night of sleep. The researchers found increased values ​​in most participants when they were not getting any sleep 5.

The researchers in the sleep study wanted to know whether the tau proteins were removed from the brain as a waste product or whether the lack of sleep caused brain damage, which then resulted in the release of the molecules. Therefore, they examined the blood for markers of neuronal damage but could not detect them. This means that lack of sleep causes tau proteins to misfold. However, they are most likely only partially removed from the brain; the rest is deposited in the organ as filaments 5.

This is alarming because such deposits have already been found in the brains of children and young adults who have not yet shown any symptoms of the disease 2. Apparently, the illness builds up over decades before it is discovered. One more reason for an early analysis of your own risk. As there is still time to change your lifestyle.

In addition to the factors already mentioned, heavy alcohol consumption also increases the likelihood of suffering from the brain disease 6. And it furthermore accelerates the progression of symptoms 7.  Of course, it is advisable for everyone to pay attention to a healthy lifestyle. However, a very early diagnosis of the increased risk could be a completely different incentive to take care of yourself and thus reduce the progress of degeneration in the brain.

What options for therapy are available?
There is still no cure for Alzheimer’s, despite intensive research. Therapies, currently in development, focus on preventing the formation of deposits or destroying them. Most approaches are based on antibodies, raised against the harmful tau proteins. This can be compared to the principle of a vaccination. However, these methods require that foreign substances must be introduced into the organ. And there is a small risk that the healthy proteins will be combated as well. This holds a potential for negative consequences as well. A sufficiently functioning remedy has not yet been found, but many are already in the advanced stages of approval. So, if effective, they could at least alleviate the severity of the disease. Early therapy is particularly important because tau filaments form in certain areas of the brain first and then slowly spread further (see figure 2). Scientists suspect a kind of contagion-like process, similar to the spread of viruses and bacteria. An early intervention could thus drastically reduce the progress of the disease 3.

It is currently not possible to predict how long it will take to find means that can prevent the onset of Alzheimer’s. However, an early test could help to find suitable candidates for testing the mode of action of drugs that tackle the very early stages of the disease. This has been difficult so far. Once a remedy is developed, family doctors can perform routine tests. When those tests indicate an increased risk of Alzheimer’s, they can recommend a brain scan. Doctors could then start treatments early and further inform these population groups about lifestyle changes that slow down the progression of the disease. The combination of the bundled efforts of Alzheimer’s research will hopefully help in the long term that the diagnosis of Alzheimer’s no longer means the slow decay of your own self.

Most important references

  1. R. Mahlberg, H. Gutzmann (Hrsg.): Demenzerkrankungen erkennen, behandeln und versorgen. Deutscher Ärzte-Verlag, Köln 2012, ISBN 978-3-7691-0563-6.
  2. Braak, H., & Del Tredici, K. (2011). The pathological process underlying Alzheimer’s disease in individuals under thirty. Acta neuropathologica, 121(2), 171-181.
  3. Congdon, E. E., & Sigurdsson, E. M. (2018). Tau-targeting therapies for Alzheimer disease. Nature Reviews Neurology, 14(7), 399-415.
  4. Pase, M. P., Beiser, A. S., Himali, J. J., Satizabal, C. L., Aparicio, H. J., DeCarli, C., … & Seshadri, S. (2019). Assessment of plasma total tau level as a predictive biomarker for dementia and related endophenotypes. JAMA neurology, 76(5), 598-606.
  5. Benedict, C., Blennow, K., Zetterberg, H., & Cedernaes, J. (2020). Effects of acute sleep loss on diurnal plasma dynamics of CNS health biomarkers in young men. Neurology.
  6. Spiegel Gesundheit „Wie starkes trinken das Demenzrisiko erhöht“. Vom 22.02.2018
  7. Heymann, D., Stern, Y., Cosentino, S., Tatarina-Nulman, O., N Dorrejo, J., & Gu, Y. (2016). The association between alcohol use and the progression of Alzheimer’s disease. Current Alzheimer Research, 13(12), 1356-1362.

Published by Katrin Heidemeyer

Katrin Heidemeyer ist Doktorandin im Bereich Biochemie an der Wageningen University and Research. Durch ihre Arbeit möchte sie das Wissen über die Spezifität von Hormon-Signalen in Pflanzen erweitern. Da ihre Interessen über Pflanzenbiologie hinausreichen, schreibt sie in ihrer Freizeit über diverse Themen. Von Ernährung zu Psychologie, der Neugierde sind keine Grenzen gesetzt.

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