With the acceleration of population aging process, aging diseases are expected to occupy a large number of medical resources in the future. Among many aging diseases, Alzheimer's disease and its dementia symptoms are the focus of global attention. On the one hand, this disease will make patients Gradually lose memory They can't take care of themselves, which also brings great pain and burden to their families; On the other hand, this disease has long faced There is no medicine to cure Only in recent years did it improve.
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Recently, a preprinted paper entitled "Causal evidence that herpes zoster vaccination prevents a promotion of dementia cases" published online has aroused extensive discussion on the Internet.
This paper found that, Some British people who are vaccinated with the common herpes zoster vaccine have reduced their dementia symptoms 。 It should be pointed out that the preprint has not been peer reviewed, so whether the research method of the paper is reliable and whether the conclusions are accurate is still uncertain. But this does not prevent us from exploring the truth and understanding what is going on.
01
A strange protein
On November 3, 1906, German pathologist Alois Alzheimer introduced a strange case at an academic conference. Since the age of 50, this patient has experienced a series of mental symptoms, including delusion, lethargy and aggression. In addition, her Memories are also being lost 。
Five years later, the patient died of illness, leaving a brain damaged by disease for Dr. Alzheimer. After dissection, Dr. Alzheimer found that the brain of the deceased was full of abnormal β - amyloid plaques and Neurofibrillary tangle , to some extent, it explains the symptoms of the patient.
Schematic diagram: β - amyloid plaques and nerve fiber tangles. Copyrighted pictures in the gallery, reprinting and using may cause copyright disputes
The report did not stir up much waves at that time, but left a name of "Alzheimer's disease" in memory of the discoverer. In 1915, Alzheimer himself died. He would not have thought that his surname was now equated with a serious disease.
For a long time, scientists have regarded these beta amyloid proteins as the cause of diseases, and believed that they killed brain cells and caused a series of symptoms. Therefore, they are also developing drugs to eliminate this protein to treat Alzheimer's disease.
Unfortunately, in the past few decades, the development of new drugs that have consumed a lot of resources has not been going smoothly. Although these drugs can effectively eliminate β - amyloid protein in the brain, they do not help improve the cognitive ability of patients Therefore, the clinical research ended with almost 100% failure.
These results can not help but make scientists re-examine the cause of Alzheimer's disease - did we get the goal wrong from the beginning? What if these beta amyloid proteins are not the cause of Alzheimer's disease, but only a symptom after the onset? If so, that could explain why drugs targeting beta amyloid continue to suffer Waterloo.
02
Microbial infection hypothesis
After the "beta amyloid hypothesis" failed in clinical research, some scientists pointed out the loopholes in this theory. For example, many people with beta amyloid deposition in their brains did not eventually suffer from Alzheimer's disease. The causal relationship between the two is no longer so clear. On the contrary“ Microbial infection hypothesis ”Came into being at the historic moment and wanted to fill the gap in the logic chain.
This hypothesis believes that β - amyloid is a consequence of brain microbial infection ——After being infected with microorganisms, the brain will deliberately produce these proteins to eliminate infection. Normally, these proteins will disappear with the passage of time. But with the growth of age, or because of some gene mutations, The brain's ability to clear beta amyloid protein will decline, leading to protein deposition , which leads to brain lesions.
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In 2019, a paper found many bacteria causing periodontitis in the brains of Alzheimer's patients. The researchers also found that the mice infected by this bacterium had more brain lesions. This finding seems to support the "microbial infection hypothesis", but the drugs designed for this theory, after years of development, also failed to prove the reliability of this hypothesis.
Nature also published a long article in 2020, which further discussed the context of the "microbial infection hypothesis", and concluded that the "microbial infection hypothesis" may be a supplement to the "beta amyloid hypothesis", rather than a substitute. To truly understand the etiology of Alzheimer's disease, we need to further understand why beta amyloid is produced and its function in the brain.
In fact, in recent years, there have been studies linking microbial infection with Alzheimer's disease, but there has always been a lack of authoritative confirmation. For this reason, some scientists even offered a reward of $1 million to anyone who can prove that "the bacteria cause Alzheimer's disease".
03
What does this paper find?
In the "microbial infection hypothesis" of Alzheimer's disease, herpes virus is one of the important suspects. In order to understand the role of this virus in dementia, the authors of this paper designed an ingenious experiment: in Wales, people can be vaccinated with a zoster vaccine called Zostavax since September 1, 2013. The vaccination of this kind of vaccine has strict requirements on age, and only people under 80 years old (born on or after September 2, 1933) can be vaccinated. Even if it was only one day short, even if it was born on September 1, 1933, this vaccine could not be vaccinated.
Compaq vaccine, photo source: Wikimedia Commons
This artificially set "one size fits all" standard provides convenience for research. Physiologically, there should be no other difference between people born the week before September 2, 1933 and those born the week after September 2, 1933. The researchers then confirmed that the two groups of people were basically the same in terms of medical insurance and other vaccination. Therefore, whether they have been vaccinated against herpes zoster has become the biggest difference between them.
Then they analyzed the effect of the herpes zoster vaccine. The first index analyzed was the number of new cases of herpes zoster. As expected, the number of herpes zoster cases in the vaccinated population has significantly decreased, which supports the effectiveness of the vaccine. Later, they began to analyze the impact of herpes zoster vaccine on dementia. No one had done similar research before, but the results shocked them - during the 7-year follow-up period, Compared with the control group (not vaccinated), the diagnosis rate of dementia in the vaccination group can be reduced by nearly 20% 。
According to this result, the researchers pointed out in the paper that, Herpes zoster virus plays an important role in the etiology of dementia 。
04
The significance of this study
In the past few years, many new drugs for Alzheimer's disease have been approved for marketing by the US Food and Drug Administration. Among them, the efficacy of Aducanumab (trade name Aduhelm) was criticized, and even doctors boycotted it after it was marketed; The effect of Lecanemab (trade name Leqembi) has been affirmed by the expert committee, which believes that it can significantly slow down the decline of cognitive ability. The action mechanism of these two drugs is to eliminate the deposition of β - amyloid, and the explanation behind the disease is still the traditional "β - amyloid" theory. The clear curative effect of the latter also indicates that the "beta amyloid hypothesis" has not been completely abandoned.
The findings of this study, based on the findings in recent years, provide a supporting evidence for the "microbial infection hypothesis", which can encourage scientists to further explore in this direction. If more evidence can be obtained, perhaps more pharmaceutical companies will invest in developing new drugs to speed up the fight against Alzheimer's disease in the future.
Of course, there are some others in this paper limit ：
First, it does not explain why the herpes zoster vaccine can reduce the onset of dementia. Although it seems that this vaccine can reduce herpes zoster virus infection and thus play a role, after all It's just a guess , not confirmed.
Secondly, the researchers also admitted that due to time constraints, they were only followed up for 8 years at most, Unable to evaluate the long-term effect of the vaccine 。
Thirdly, the follow-up period of this study coincided with the COVID-19 epidemic, and a considerable number of patients were not excluded Because the epidemic has not been diagnosed in time , affecting the results
Finally, their research is also limited to a kind of vaccine of Compaq vaccine, Results cannot be extrapolated to all similar vaccines 。
05
summary
In general, this study provides another evidence for the "microbial infection hypothesis" of popular Alzheimer's disease, and provides a directional reference for future prevention and treatment. But we also want to remind readers that the results of this study have not yet been confirmed, Don't simply think that vaccination against herpes zoster can prevent Alzheimer's disease 。 We also look forward to seeing more convincing research on the relationship between Alzheimer's disease and microbial infection in the future.
reference:
[1] Causal evidence that herpes zoster vaccination prevents a proportion of dementia cases
[2] The discovery of Alzheimer"s disease
[3] Are infections seeding some cases of Alzheimer’s disease?
Author: Ye Shi, creator of popular science
Reviewed by: Liu Yuanyang, Chief Pharmacist of the Fourth Medical Center of the PLA General Hospital
Editor in charge: Cui Yinghao Ding Jia
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