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Dementia: from brain to brainProteins involved in the development of Alzheimer's disease may be transmissible, but not the disease itself.

Denervated. Misfolded amyloid proteins accumulate (red) in brains of Alzheimer's patients (left), then the. Photo: Focus/A. Pasieka

Fold incorrectly, form clumps and deposit in the brain. Proteins called beta-amyloid (Aβ) play an important role in the development of Alzheimer's disease. Gradually, the insoluble deposits clog the spaces between neurons that inevitably die in the disease. Now there are new indications that these protein fragments could be transmissible from person to person in rare cases, as John Collinge of University College London and his colleagues report in the scientific journal "Nature" report.

The administered growth hormones brought death

In an earlier study, the British researchers had examined patients who had died of Creutzfeldt-Jakob disease (CJD). All of them had been small in stature as children and had been treated with growth hormones, which at that time were extracted from the brains of deceased persons. However, some hormone preparations were contaminated with prions, the pathogens that cause CJD.

However, in addition to prions, the researchers also found altered blood vessels in the patients' brains. The patients had the first signs of a disease called cerebral amyloid angiopathy (CAA) (CAA), which often occurs together with Alzheimer's disease. In this case, misfolded Aβ-proteins are deposited on the inside of the vessel walls. Even small amounts, so-called "seeds (seeds), can cause more and more of the proteins to clump together into a plaque, like a snowball, and stiffen the walls of the veins. One consequence can be cerebral hemorrhages, which can also be fatal.

For the scientists, these changes in the patients' brain vessels were the crucial clue that the protein plaques – just like the prions – might also have been transmitted via contaminated medical devices.

The proteins also accumulated in the brains of mice

There was only one way to find out. They re-examined the hormone preparations administered at the time, which have been lifted until now. And they found what they were looking for: Some of the samples contained high levels of two different Aβ variants and tau proteins, which researchers also link to the development of Alzheimer's disease. To find out whether the proteins might actually have been responsible for the changes in the brains of the deceased, Collinge and colleagues injected the proteins directly into the brains of mice.

In the brains of those animals that had received hormone preparations, the researchers found Aβ deposits after a few months, and mainly in the vessels. But not in the mice that had not been given hormones. "This shows that the hormone batches of that time contained Aβ-proteins capable of accumulating into plaques in mice,", write the researchers. They do not rule out the possibility that the misfolded proteins could also be transmitted to humans in isolated cases via contaminated medical devices.

No evidence of transmissibility of Alzheimer

Does this mean that Alzheimer's disease can also be transmitted from person to person – for example, through contaminated surgical instruments?? "This is exactly the conclusion that would be completely wrong", says Frank Heppner, director of the Institute for Neuropathology at the Charite in Berlin. Basically, the researchers would have only shown that the vascular disease CAA is transmissible in mice. Alzheimer's disease is not only characterized by the amyloid plaques found, but also by the accumulation of tau proteins in the brain and the development of dementia. "Neither was the case in the patients who died at the time, just as the researchers have now found in the mice."

In addition, genetically modified animals were used in the experiment, which react particularly sensitively to the modified proteins and attract them "like a magnet" attract. It's different in normal mice, which is another reason why the experiment is unlikely to be transferable to humans, says Heppner.

Furthermore, the researchers also write, there is no evidence from population studies that Alzheimer's is transmissible, for example through blood transfusions. They also found no increased incidence of the disease in relatives or staff who had cared for Alzheimer's patients.

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