A mathematical model that unravels the mechanisms of disease formation, with the aim of creating drugs that act when it is not yet too late
Alzheimer-Perusini disease, also called Alzheimer’s disease , is the most common type of dementia, affecting 50 million people worldwide. The number is expected to triple in less than 30 years. In Italy there are one and a half million Alzheimer’s patients, a figure released by a report by the Italian Alzheimer’s Federation, which states that in 2050 the number will rise to 2.3 million, given the exponential growth rate of the population affected by the disease over the years : Italy is the longest-living country in Europe, so to speak, with 13.4 million over-60s, equal to 22% of the population. Living this strong aging of the population, the people affected by the disease are destined to increase progressively.
A distinction must be made between senile dementia and Alzheimer’s, which are often confused even if they are two different conditions: dementia is a natural condition of senility, of aging, Alzheimer’s is instead a disease, a disease, a chronic and degenerative condition direct cause of death, as opposed to senile dementia. The two are often overlapped and confused, perhaps because they have the age of the sufferer as a common point. As in dementia, age is the main influencing factor in Alzheimer’s disease, but family genetic history also has an impact on the development of the disease.
Having said this, we know that as the patient ages, different symptoms can develop such as: aphasia, disorientation, sudden changes in mood, depression, inability to take care of oneself, behavioral problems. This leads the subject to isolate himselfby society and its family context. Gradually, basic mental abilities are lost. Although the rate of progression can vary, the average life expectancy after diagnosis is three to nine years. The cause and progression of the disease is not yet well understood. Research indicates that the onset of the disease is closely associated with a class of proteins, amyloids, stable components of our immune system, which in the disease aggregate into plaques and clusters in the brain called neurofibrillaries. What is not yet known, at least until today, is the main cause of the degeneration of these proteins.
The research team at the University of York’s School of Physics, Engineering and Technology observed two variants of the amyloid protein, both widely present in Alzheimer’s patients. These proteins condense into structures resembling drops of water which merge into clusters that compromise the normal functioning of the brain. Amyloid proteins begin to aggregate about 10-15 years before the first symptoms appear.
What is not yet clear, however, is the mechanism by which the “droplets” become a single mass. Although amyloid proteins are believed to be an important component of the immune system, it is the abnormal version of the protein that is of concern because, when it clumps together, it becomes powerful and harmful, interfering with normal brain activity. “Understanding how amyloid clumps form at the precise molecular level can help us design better drugs that can fight Alzheimer’s disease at the earliest possible stage,” said Alzheimer’s Research fellow Dr. Steve Quinn UK and professor of biophysics at the University of York. The “ amyloid hypothesis” explains that Alzheimer’s could be caused by the deposition and accumulation of amyloid compounds in the brain tissue, causing the pathogenesis, ie, the development of the disease.
For these reasons, the researchers have staked everything on a mathematical model they studied and developed, to find out how toxic proteins aggregate in the brain during the early stages of the disease and to act on this formation in the pharmacological treatment of the disease. The research team noted that this is the first time the details of the early stages of amyloid cluster formation have been examined.
The road to future treatments
The York researchers said the discovery could be used to study future therapeutic protocols. “The properties of large preformed clusters have been studied extensively, but until now it has been difficult to assess the molecular-level details of the initial assembly stage,” said Dr. Charley Schaefer, lead author of the study. Researchers hope that understanding exactly how toxic protein clumps form will allow them to develop targeted drug treatments in the futureto discourage the formation of amyloid clusters in the early stages of Alzheimer’s disease. Currently, the therapeutic treatments used offer small benefits in terms of symptom relief and can partially slow down the course of the pathology; Although over 500 clinical trials have been conducted to identify a possible treatment for Alzheimer’s, no treatments have yet been identified that stop or reverse the course. In this context, therefore, the study by the York researchers represents a great step forward in the treatment of the disease.