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Forgetting, one of the most sad diseases

Alzheimer’s disease is a condition that makes countless people to feel fear and power from deep inside. Perhaps people think that this is only an unfortunate disease that the old people will have. But in fact, the ageing of the human brain starts at the age of 40. The brain shrinks by about 5% every 10 years. After the age of 70, this shrinking process will accelerate. Alzheimer’s disease is not part of normal aging, and young adults in their 40s also suffer from this disease.

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So far, it has no cure and is diagnosed as suffering from Alzheimer’s disease. There is not much chance of struggle. It can only be allowed to affect one’s emotions, memory, thinking and behavior. Slowly forgotten all memories of love and life. People are more and more aware of the terrible disease, but in the absence of a cure, more and more people are only desperately hoping for better predictions of Alzheimer’s disease.

Terrible β-amyloid

Scientists are also racing to find ways to treat Alzheimer’s disease, hoping to use new methods to reduce the number of people affected by this tragic illness. There are more than 100 treatment methods that have been used in clinical trials, including not only the MRI technique used to diagnose early Alzheimer’s disease, but also the ability to specifically target the brain called beta-amyloid. (A-β) antibody.

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Recently, researchers at the National Center for the Study of Longevity in Japan (NCGG) have made new discoveries and may be able to determine whether or not the person is at risk of developing Alzheimer’s disease simply by measuring A-beta in the blood. Removal of A-beta plaques in the brain is a major strategy for the treatment of Alzheimer’s disease. NCGG’s current discovery uses the measurement of plasma A-beta levels to determine whether there is accumulation of A-beta in the brain. Researcher Katsuhiko Yanagisawa and his colleagues developed a prototype of this biomarker test and published the results in the January 31 issue of Nature.

○ A type of viscous protein known as β-amyloid (a part of Campanula-like ball in the figure) can begin to accumulate in the brain decades before the onset of Alzheimer’s disease. | Image credit: SELVANEGRA/ISTOCKPHOT

A-beta is a viscous protein that can accumulate in the patient’s brain decades before the Alzheimer symptoms began (20-30 years ago). Normally, the detection of A-beta plaques in the brain needs to be accomplished by techniques such as brain scanning or spinal puncture. There is increasing evidence that the level of A-beta in the blood can be used to predict whether a person’s brain has these plaques.

This new result is a good example of a smaller study completed by another research team in 2017. Randall Bateman, an Alzheimer’s disease researcher at the Washington University St. Louis School of Medicine, who was the leader of the 2017 study, said: “This is an excellent proof of our findings. This tells us that we can continue with confidence. Advance this test method and believe that there will be good results.”

 

Creating such a test has always been very challenging: in contrast, A-beta floating in the blood is far less than the accumulation in the brain. And in the past many studies did not find a consistent correlation between the two.

In the new study, the researchers used measurement technology as a more sensitive measurement technique than most previous studies—mass spectrometry, which detected smaller amounts of protein. Moreover, the researchers did not directly measure the total amount of this protein in the blood, but instead calculated the ratio between different types of β-amyloid. The ratio of precursor protein (APP) 669-711 to (A-β) 1-42, and the ratio of (A-β) 1-40 to (A-β) 1-42, respectively, of A-β.

They analyzed two separate sets of samples, one set consisting of 121 Japanese participants for discovery and the other consisting of 252 Australian participants for validation. Both groups were between 60 and 90 years of age. They provided their brain scans and blood samples as analysis data to researchers. In each group of participants, some were true Alzheimer’s patients, some had mild cognitive impairment without Alzheimer’s disease, and some had no cognitive function.

Researchers found that by analyzing the ratio of different A-beta, they could distinguish between those with A-beta plaques in the brain and those without A-beta plaques. They found that using this method to predict the presence of A-beta plaques in the brain is as accurate as 90%.

The significance of early detection

At present, we are still in a situation that neither cures Alzheimer’s disease nor slows or stops the disease from worsening. Therefore, even if the signs can be confirmed at an early stage, the subsequent progress of the disease cannot be improved. However, early detection of this method is valuable because it helps scientists monitor the formation of A-beta in the brain as early as possible. In the words of Steven Kiddle, a Cambridge bioscientist, blood tests can make it easier for researchers to discover those who might be candidates for early intervention clinical trials, which will greatly advance the monitoring of A-beta in the brain.

Finding it too late is also one of the problems in the prevention experiments for Alzheimer’s disease. Most patients are only about 60 years old before they are identified as A-beta in the brain. Early detection may therefore provide scientists with more research directions, and many pharmaceutical companies have also started trials for younger people with Alzheimer’s disease. In an interview in 2017, Phyllis Ferrell, vice president of the US pharmaceutical company Eli Lilly and Company, stated that the focus of research on Alzheimer’s disease is now gradually being focused on detecting and preventing prematurely. She said: “This is like studying cancer. We need to find it at an early stage, not at a later stage.” When the symptoms that are visible to the naked eye have already emerged, it may be time for the late stage of surgery.

Although Professor Kiddle from Cambridge University did not directly participate in this discovery, he believes that the new results have brought a lot of hope. But before it is officially used in clinical practice, scientists need to further refine and upgrade this test. Similarly, there is another problem with this test, which is cost. At present, we cannot determine whether this blood test is more affordable than brain scan or spinal sampling. The authors of the paper also stated that this technique will require larger and longer-term studies to demonstrate how accurate blood tests can determine the level of A-beta in the brain. However, for those who may suffer from such a cruel disease in the future, it is good news that deserves attention and expectation.

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