Subverting cognition, can dementia be transmitted from person to person? It is really unexpected that it can spread in this way

Alzheimer's disease is a serious neurodegenerative disease that affects about 300 million people worldwide, bringing a significant medical burden. If the disease can be effectively prevented and treated, it will undoubtedly have great significance for the whole society. However, despite the significant progress made in this field of research in the past few decades, scientists have not yet fully understood the cause of this disease.

Recently, a study published in Nature Medicine, a journal under Nature, found that Alzheimer's disease can actually be transmitted from person to person. Although the sample data of this study is very small, it still provides a new perspective for everyone to understand this disease.

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Alzheimer's disease and protein deposition

In November 1906, German doctor Alois Alzheimer reported a strange case at an academic conference: a 50-year-old woman seemed to have obvious mental problems. Not only did she have severe memory impairment, but her thinking suddenly became confused and she had difficulty communicating. After the patient died, an autopsy found strange lesions in her brain, with many plaques and neurofibrillary tangles.

Later, people named the disease after his surname, namely Alzheimer's disease. Now people have found that these pathological changes are caused by "wrong proteins". Misfolded beta-amyloid protein causes plaque deposition in the brain, while tau protein causes tangles. These problematic proteins have become the focus of later scientists' research. It is generally believed that these lesions appear in the patient's brain before symptoms appear, so the current mainstream view is that they are the main cause of the disease.

So where do the initial misfolded proteins come from? The answer is complicated: some may be due to one's own gene mutations, some may be purely due to aging, and some may be infection by foreign pathogens. However, this Nature Medicine paper clearly shows that they may also come from other humans.

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Hormones from corpses

In this study, scientists looked to the UK. From the 1950s to the 1980s, a group of patients suffering from "pituitous insufficiency" received growth hormone treatment. Limited by the production technology at the time, people were unable to produce this hormone on a large scale, and the solution was to use it on people, to extract it from the pituitary glands of human corpses and then use it for treatment.

In the more than 30 years of using this technology, people have gradually realized that this treatment may not be safe. Just as pathogens carried by blood donors can be transmitted to other people through blood, if there are transmissible pathogens in the brain used to extract growth hormone, it will also affect the patients receiving treatment.

Creutzfeldt-Jakob disease is a brain disease that can be spread with injections of such growth hormones. Similar to mad cow disease, Creutzfeldt-Jakob disease originates from the transmission of prions. Prions are essentially misfolded proteins that aggregate in the brain, affecting its structure and function. There is no cure for Creutzfeldt-Jakob disease, and patients generally die within a year of diagnosis. For safety reasons, the use of growth hormones from human corpses was finally banned in the UK around 1985. However, the aftermath of this treatment continues to this day.

Alzheimer's disease can be contagious

Earlier, researchers found a large amount of beta-amyloid protein in several batches of growth hormone that have been sealed up to this day. This immediately alerted them: If the prions in growth hormone can cause the spread of Creutzfeldt-Jakob disease through injection, then these growth hormones mixed with beta-amyloid protein will not also cause Alzheimer's disease?

To answer this question, researchers investigated eight British people who had received such hormone treatments as children. Five of them had confirmed severe dementia symptoms in adulthood, with the earliest symptom appearing at the age of 38, much earlier than the average age of onset of Alzheimer's disease. Two of the other three also had mild cognitive impairment, and only one currently had no symptoms.

During the study, two patients died, and autopsies confirmed that they had typical lesions of Alzheimer's disease in their brains. Through family history analysis, the researchers also ruled out the possibility of genetic causes. The only remaining cause was growth hormone mixed with misfolded beta-amyloid protein. These proteins, like seeds, continued to spread in the brains of patients receiving hormone treatment, and finally caused Alzheimer's disease.

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Implications for research fields

Previous animal studies have shown that these misfolded beta-amyloid proteins, like prions, induce Alzheimer's disease-related pathological features through a mechanism similar to "mad cow disease." This study further supports this theory through real-world humans.

However, it should be noted that this is a special event caused by human manipulation, which is almost impossible to repeat in today's life, and the number of potential cases will not continue to increase with the termination of this treatment.

The researchers also specifically reminded that daily care for Alzheimer's patients will not lead to similar infectious incidents, so people do not need to worry.

But from the perspective of understanding the disease, it actually reveals an important step in the onset of Alzheimer's disease, that is, as long as there is misfolded beta-amyloid protein, it may sweep the entire brain like wildfire. On the one hand, this emphasizes the importance of completely eliminating these pathogenic proteins, and on the other hand, it urges researchers to speed up the search for the source of the initial misfolded protein in order to achieve early detection and prevention as much as possible.

References

[1]EvidenceforiatrogenictransmissionofAlzheimer'sdisease,https://www.nature.com/articles/s41591-023-02768-9[2]IatrogenicAlzheimer'sdiseaseinrecipientsofcadavericpituitary-derivedgrowthhormone,https://www.nature.com/articles/s41591-023-02729-2

Author: Ye Shi Popular Science Creator

Reviewer: Tang Qin, Director and Researcher of the Science Popularization Department of the Chinese Medical Association