What can save you—Alzheimer’s disease which cannot be cured?

Alzheimer's disease (commonly known as senile dementia) is a disease that is a little far from us, but it is a stubborn disease that many elderly people cannot avoid. How should we deal with it? This may be a problem that both ordinary people and academic circles have been concerned about. Today we will talk about this issue systematically.

01. Alzheimer's disease: When we start to forget

Poor memory is often an excuse we like to make for ourselves, but if this poor memory becomes a real disease, then it may not be good.

This is an important manifestation of Alzheimer's disease. As a neurodegenerative disease, the typical manifestation of Alzheimer's disease is memory loss. Imagine that you will gradually forget many things. First, short-term memory becomes worse, then you start to forget recent events, and then forget more distant things, until you can't remember your colleagues, friends, and even children. What a terrible thing. Moreover, Alzheimer's disease is accompanied by many problems such as decreased speech ability, mobility, and cognitive impairment until you completely leave this world.

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As a disease that has been recorded very early, it was not until 1901 that German psychiatrist Alzheimer first named the disease after himself. In the following years, he discovered that the disease was not rare, but was widely present in the population.

According to research, Alzheimer's disease is a typical disease that increases with age. For example, in the United States, the incidence of Alzheimer's disease in the 60-74 age group is 5.3%, while in the 74-84 age group, this proportion rises to 13.8%, and in people over 85 years old, the proportion of Alzheimer's disease will be as high as 34.6% [1]

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Today, both doctors and scientists will tell you that Alzheimer's disease must be detected and treated early.

Behind this empirical truth lies a painful problem in Alzheimer's disease research and drug development: Alzheimer's disease cannot be cured.

02. Alzheimer’s disease cannot be cured

In the past hundred years, our science and technology and medicine have made great progress. Even in the field of cancer, which is feared by everyone, we have made considerable progress. A series of strategies such as surgery, chemotherapy, radiotherapy, and immunotherapy are all improving. There is even an immunotherapy that can completely cure special blood tumors.

However, for Alzheimer's disease, a disease that has been discovered for hundreds of years, our means of treating it are surprisingly limited, or even "helpless." This is all due to the fact that our research on Alzheimer's disease has been full of setbacks.

03. Why do people get Alzheimer’s disease?

Why do people get Alzheimer's disease? The earliest observations of brain slices from Alzheimer's patients provided us with a profound understanding.

Compared with normal people, the brains of people with Alzheimer's disease show obvious atrophy. From a pathological perspective, the most significant pathological feature of Alzheimer's disease is the presence of a large number of senile plaques composed of amyloid protein (Aβ) in the brain, which has also triggered the most important field of research on the mechanism of Alzheimer's disease: the β-amyloid hypothesis. That is, the Aβ amyloid protein produced in the brain is toxic and can continuously damage the brain, eventually causing degenerative changes in the brain [4].

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This has in fact been confirmed in experiments.

Aβ is derived from the gene encoding amyloid precursor protein (APP). Under normal circumstances, APP is cleaved by α-secretase and β-secretase to form a soluble s-αAPP peptide, which is then further cleaved into p3 peptide. However, in rare cases, APP protein is cleaved by β-secretase and γ-secretase to form Aβ [5].

Depending on the difference in the cleavage position of γ-secretase, Aβ proteins composed of 40 and 42 amino acids (Aβ40, Aβ42) will be formed. These two proteins are important proteins that cause AD, especially Aβ42, which is easy to aggregate and has strong cytotoxicity, and finally forms amyloid plaques in the brains of AD patients.

Conversely, if the production of Aβ is reduced, the incidence of Alzheimer's disease can be reduced. For example, a rare mutation A673T has been found on the Aβ gene, which can reduce the production of Aβ, thereby reducing the incidence of AD in the population and having a protective effect on the cognitive ability of the elderly [6].

It all seems perfect, but when scientists try to clear Aβ from the brain, either through drugs that directly clear Aβ or indirectly by affecting β-secretase and γ-secretase to reduce Aβ production, the results are that they cannot solve Alzheimer's disease.

Of course, many people may think of the recent Aβ56 fraud incident, and some even think that this destroys the basic hypothesis of Alzheimer's disease. In fact, they think too much. Aβ56 is at most a small branch of the Aβ hypothesis in Alzheimer's disease. The real Aβ hypothesis itself is still the most basic hypothesis that can stand the test.

Of course, some scientists have also tried to find other mechanisms of Alzheimer's disease, such as targeting neurofibrillary tangles (NFTs), a type of neural change caused by tau protein [7], and even developed corresponding drugs, but the result is still the same: failure.

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In addition, some scientists have proposed the microbial infection hypothesis, which is based on the evolutionary origin of the Aβ protein structure and the correlation between the incidence of oral diseases and Alzheimer's disease, but we cannot find a solution at present.

It can be said that the exploration of the mechanism and treatment of Alzheimer's disease has been ongoing over the years, but it has been met with repeated failures.

Of course, this has not stopped people from developing drugs for Alzheimer's disease. For example, the website of CDE (Center for Drug Evaluation of the State Food and Drug Administration) still shows the ongoing research on Alzheimer's disease drugs. Perhaps in the future a real drug to treat Alzheimer's disease will be found. If you are interested, you can go directly to the official website of CDE to make relevant inquiries.

As for the current Alzheimer's disease, the choline hypothesis that was first proposed, that is, Alzheimer's disease is caused by a decrease in the neurotransmitter acetylcholine. This theory, which is considered to be wrong, has become the only straw for treating Alzheimer's disease. Currently, the drugs for Alzheimer's disease are basically targeting choline.

However, this drug only has a certain relieving effect in the early stages and is ineffective in the middle and late stages.

Therefore, for Alzheimer's disease, early detection and early treatment may be the only option.

04. Early detection and early treatment may be the only way at present

Nowadays, early detection and early treatment of Alzheimer's disease are basically the consensus in the industry. So what are the early signs of Alzheimer's disease?

It is generally believed that the early symptoms of Alzheimer's disease are relatively difficult to judge, but we can still find some signs. The most typical one is memory loss. Although memory loss is a common phenomenon with age, if a person's memory loss is more obvious, then it is worth paying attention to.

In addition, changes in personality may also be one of the important signs of Alzheimer's disease, so if the elderly person's temperament suddenly changes, you should pay attention.

In clinical practice, after years of summary, there is also a set of relatively reliable judgment standards, such as the NINCDS-ADRDA standard established in 1984. Through this set of testing standards, Alzheimer's disease can be distinguished to a large extent.

Early treatment currently mainly adopts cholinergic drugs, such as AchE inhibitors, nicotinic receptor modulators and glutamate receptor antagonists, which can significantly improve the early symptoms of Alzheimer's disease. Even for normal people, this drug can reduce the risk of Alzheimer's disease. In addition, antidepressants are also believed to have a certain therapeutic effect on early Alzheimer's disease, and the specific treatment is subject to the doctor's advice.

Of course, in addition to drug treatment, there are a series of measures in reality that can reduce the incidence of Alzheimer's disease.

For example, physical exercise. Studies have found that physical exercise, especially aerobic exercise, can significantly improve memory and cognitive function in Alzheimer's disease.

For example, some intellectual exercises, such as reading, crossword puzzles, and chess, can also improve symptoms of Alzheimer's disease.

These strategies, combined with early treatment, can alleviate early symptoms and reduce the incidence of Alzheimer's disease in normal people.

In addition, prevention is also a good idea.

05. How to prevent it?

So how do we prevent Alzheimer's? On the one hand, we should try to reduce risk factors and pay special attention to groups with possible risks. For example, we should pay special attention to certain genotypes.

Typically, individuals with the APOE 4 genotype need to be given special attention, as this genotype has an incidence rate of Alzheimer's disease more than ten times higher than that of APOE2 [9]. The TREM2 gene is also a gene found in recent years to be associated with the risk of developing Alzheimer's disease [10].

For example, some diseases need special attention, such as cardiovascular and cerebrovascular diseases, stroke, hypercholesterolemia, hypertension, diabetes and smoking, which are high-risk factors for Alzheimer's disease, so these disease groups should also be paid special attention to.

On this basis, the study found that many small details are actually related to the onset of Alzheimer's disease.

For example, a healthy lifestyle, good eating habits, and low psychological stress can all reduce the incidence of Alzheimer's disease.

It can be said that Alzheimer's disease is a very serious disease, but in reality, the attention paid to it is far from enough. And due to the lack of relevant drugs and treatment measures, the response to Alzheimer's disease must be early detection and early treatment. The earlier the intervention, the more likely it is to reduce the incidence of Alzheimer's disease.

This article will be included in the "People Trapped in Time - Alzheimer's Disease Special Topic".

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