Study of Alzheimer's disease (1)
Evgeny Rogaev, Post-science
Aging is the main factor in many diseases. It is known that the cause of most deaths is diseases associated with aging. We are especially interested in those related to the brain – degenerative or neurodegenerative diseases, such as dementia – loss of memory and intelligence with age. If we go back 100 years and look at the patients of any psychiatric clinic, we will notice that at least 20-30% of patients have dementia. It looks strange, since these people were not of advanced age. Then it becomes unclear what kind of disease it is. It is important to note that these forms of dementia no longer exist in our time. Most of the diseases that we now call dementia 100 years ago were associated with neurosyphilis – a disease that affects the brain for 16-20 years, primarily the frontal and parietal cortex. As a result, certain forms of dementia begin to develop. Neurosyphilis was widespread before the discovery of antibiotics. Subsequently, the Nobel Prize was awarded for the treatment of this disease.
Austrian psychiatrist Julius Wagner-Jauregg was engaged in the treatment of the mentally ill. One of his methods of treatment was that he took a donor with malaria and injected blood into a patient with neurosyphilis. The patient developed fever, malaria plasmodium died from fever, and the patient was cured of syphilis and neurosyphilis. Wagner-Jauregg received the Nobel Prize for this research, and after the discovery of antibiotics, the disease became curable. Now dementia manifests itself as Alzheimer's disease, which develops in old age. Previously, the maximum life expectancy was less, so Alzheimer's disease was not so well known. Today we have more information about the molecular mechanisms of Alzheimer's disease. I will historically describe the course of its study.
Alzheimer's disease is named after the German neuropsychiatrist Alois Alzheimer, who in 1903 described the first case of the disease. The patient was under 60 years old, and the first signs of the disease were strange: a feeling of jealousy towards the spouse, which developed into mental disorders and memory loss. To any question from the doctors, the patient called her name Augustine. From a medical point of view, such signs are called aphasia, aprosexia, agnosia. These clinical terms denote misunderstanding of words, inability to plan and structure words, inability to recognize surrounding objects, faces. According to clinical questionnaires, there are three types of reliability of the definition of Alzheimer's disease: possible (Eng. possible), probable (Eng. probable) and definite (eng. definitive) form. But with the use of MRI technology, the diagnosis becomes better, it becomes possible to see amyloid plaques – a sign of Alzheimer's disease. Post-mortem signs also accurately indicate the presence of the disease and usually coincide with clinical questionnaires.
The main task of doctors is to separate Alzheimer's disease from other types of dementia. There are also frontal-frontal, multi-vascular dementia, dementia associated with other degenerative diseases. Alzheimer's disease is a unique case of a complex disease, where it was possible to reliably detect genes and decipher the molecular mechanism of the disease. This is a textbook example of how you can study the mechanism of a complex disease. For schizophrenia, the mechanism of the disease is still unknown. The main task of doctors is to separate Alzheimer's disease from other types of dementia.
Why was the disease named after Alzheimer's? After the death of the first patient, he investigated other cases. And during histopathological analysis, he was able to see on brain slices that patients have black accumulations, amyloids. Previously, they were found in patients with epilepsy, but Alzheimer described other types. These amyloids accumulate in the intercellular space. Now we know that amyloid plaques consist of amyloid peptides – short pieces of proteins 40-42 amino acids long. It turned out that amyloids become fibrilogenic, that is, they stick together and dissolve very difficult, accumulating in the brain like garbage. Another histopathological sign that Alzheimer discovered is the accumulation of another type of protein. At that time, the true composition of the plaque was unknown, so Alzheimer's just made an observation. In the neurons, he saw neurofibrillary tangles, twisted microtubules. It is now known that these are chemically modified proteins – tau proteins that carry out the transport of other proteins, but in case of disease they are twisted in neurons. Here are two signs of Alzheimer's disease: neurofibrillary tangles, amyloid plaques.
With his observations, Alzheimer showed that neuropsychic disease is associated with a change at the organic level. In schizophrenia, there are no such obvious changes confirmed for different patients. Alzheimer presented this case at the German congress of psychiatrists of the Southwestern Society of Psychiatry, but after his presentation, not a single question was asked, as it was not interesting. No one could have thought that this rare case would turn out to be the most common brain disease in old age. But this happened because the number of the elderly population is growing every decade, and its proportion will increase.
If we take a group of people after the age of 85, then 50% in this group already have Alzheimer's disease or will soon get sick. Even today there are no medications that treat the mechanism of this disease. Previously, there was a lot of propaganda for the study of this disease in the United States. To some extent, I was involved in fairly early genetic studies of Alzheimer's disease. We were able to detect molecular genetic markers. Simultaneously with our research, families with Alzheimer's disease began to gather in the United States to check the relationship of the disease not only with age, but also with genetic factors. It was genetic research that allowed us to unravel the molecular cause and mystery of Alzheimer's disease.
About the author:
Evgeny Rogaev – Doctor of Biological Sciences, Corresponding Member of the Russian Academy of Sciences, Head of the Laboratory of Evolutionary Genomics of the N. I. Vavilov Institute of General Genetics, Head of the Department of Genetics of the Faculty of Biology of Moscow State University, University of Massachusetts Medical School.
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