Alzheimer's disease and mad cow disease: what is common?

Alzheimer's is contagiousPyotr Smirnov, "Newspaper.
Ru»Alzheimer's disease may turn out to be a prion infection –at least half of it.

Defective tau protein, the tangles of which destroy nerve cells, is able to transform into a normal tau protein, just as prion mad cow proteins do.

Terrible infections that can spread across the planet in two weeks, and metabolic disorders, as medicine develops, begin to give way to age–related diseases associated primarily not with external factors and congenital mutations, but with internal ones - in particular, with the gradual accumulation of errors in cell division. It is age that is considered the main risk factor for the development of tumors and neurodegenerative diseases.

For neoplasms, however, back in the century before last, it was possible to demonstrate the role of carcinogens, and in the middle of the last – radiation and even viruses. But the causes of Alzheimer's or Parkinson's disease remain very vague to date.

Markus Tolnay from the University of Basel and his colleagues from Tubingen and Cambridge found "prion traits" in Alzheimer's disease – when introduced into the brain, a mutant tau protein turns into a similar normal tau protein.

Brain disorders in this disease are primarily associated with the deposition of two types of plaques – larger beta-amyloid and smaller tangles of the so-called tau protein. In the case of amyloid, the picture is more or less clear: first, a full-fledged protein is synthesized, but instead of participating in the work of neurons, for unknown reasons, it is cut into short chains, which form plaques. Until recently, beta-amyloid was given a leading role in this pathology, but recent studies have paid more attention to tau protein.

The Tau protein undergoes excessive phosphorylation and, instead of working as part of the cytoskeleton – a kind of rails along which organelles move inside the cell, forms tangles that first destroy intracellular transport, and then contacts between neurons. To top it all off, plaques and tangles contribute to the development of an inflammatory reaction, which only aggravates the situation. The further picture, unfortunately, is familiar to many of those over 80, firsthand: progressive loss of both short-term and long-term memory, urinary incontinence, impaired fine motor skills and writing, speech disorders and apathy.

Apparently, the authors of the publication in Nature Cell Biology were reminded of biochemical changes in another pathology of the brain – Creutzfeldt–Jakob disease caused by prions. Getting into the body with food (one of the assumptions is the meat of mad cows), the prion protein penetrates into the brain, where it changes normal proteins in its image and likeness. It is implied that this is the same protein, but in two forms – a prion "sick" and a slightly different normal "healthy" one, even performing some function. That is, the infectious agent in this case is a single prion protein without any DNA or RNA inclusions, multiplying not like protozoa, bacteria or even viruses, but due to "recruitment" – the rearrangement of proteins similar to it.

To test their hypothesis, Tolnay and co–authors first genetically modified mice, creating two lines - with a defective tau protein and with a normal tau protein. In the second case, the mice developed normally, tangles were not formed in their brains, and the rodents coped with all the tasks normally. But the mutant form led to the deposition of exactly the same tangles, which affected all brain functions. But this only proved the role of mutation, that is, an innate factor.

Scientists achieved the "prion" effect in the second experiment, when they isolated tangles with defective tau protein from the brains of "sick" mice and injected them into certain areas of the brain of healthy rodents, which already had normal human tau protein. For several months, the concentration of defective tau protein increased in all vital structures of the brain, not just at the injection site.

In the event that the injection was made into the brain of genetically unchanged rodents, that is, those who lacked normal human tau protein, tangles of defective tau were traced for some time after administration, but spread throughout the tissue did not occur. This is what allowed scientists to talk about the prion nature, when a "bad" protein needs a good one to spread. However, for final conclusions, they still need to show how the "recruitment" itself takes place, whether the defective protein can get out of the bloodstream and whether it persists during digestion.

If the "infectious" nature can be confirmed, it is possible that patients with "alzheimer's" may soon become younger, the same applies to rarer taupathies characterized by deposition of tau protein, but not amyloid plaques - Peak's disease and other neurodegenerative disorders.

As for the practical significance, unlike in the Western world, Alzheimer's disease is not such a large-scale problem for domestic healthcare. Perhaps by the time scientists figure out all the details of its occurrence and develop a couple of ways to effectively treat the causes, not the effects, our average life expectancy will have already grown to the "required" 80 years.

Portal "Eternal youth" http://vechnayamolodost.ru/08.06.2009