A new study, published in the journal Advances in Science, I used it for the first time human data to quantify the speed of the various processes that lead to Alzheimer’s disease. The international team, led by the University of Cambridge (UK), found that this neurodegenerative disease develops very differently than previously believed, which could have implications for the development of possible treatments, according to the authors.
The researchers found that instead of starting from a single point in the brain and starting a chain reaction that causes brain cell death, Alzheimer’s disease affects different regions of the brain early. The speed with which the disease kills cells in these regions, through the production of toxic protein groups, also determines the speed at which it propagates.
The team found that, instead of starting at a single point in the brain and starting a chain reaction that causes the death of brain cells, as previously believed, Alzheimer’s affects different regions of the brain early.
In the study they used brain samples post mortem of patients with Alzheimer’s and PET scanner images (positron emission tomography) of living patients.
As explained to SINC, georg Meisl, of Yusuf Hamied Chemistry Department, Cambridge and first author of the work, “to ensure that the conclusions they were general, we used several different datasets, measured with different methods and information from previous studies. Also new data from Cambridge Brain Bank, which maintains records and samples of patients with neurodegenerative diseases, including Alzheimer’s “
Patient data included from those with a cognitive impairment mild, even those who have suffered from the disease in its entirety, in order to track the tau aggregation, one of the two key proteins involved in the disease.
In Alzheimer’s disease, tau and another protein called beta-amyloid accumulate in the form of tangles and plaques – known as protein aggregates– which causes brain cell death and brain shrinkage. The consequences are memory loss, personality changes and difficulty in performing daily functions, among others.
Chemistry, Better Measurements and Mathematical Modeling
“Alzheimer’s disease is very complex. So on our team, we’re trying to improve your research by contributing ideas from a different discipline: chemistry. To make this study possible, we needed best measures for get detailed information about the disease, such as a specific type [escáner] of PET, and a new mathematical model”Meisl points.
The expert says that over the last decade his group “developed the ideas that led us to this model, starting the process in a test tube and then examining increasingly complex systems, until finally we were able to analyze patient data”.
The authors noted that the mechanism that controls the rate of disease progression is the replication of protein aggregates in individual brain regions, not the propagation of aggregates from one area to another.
By combining the different data sets and applying them to this mathematical model, the researchers found that the mechanism that controls the progression rate of the disease it is the replication of aggregates of proteins in individual brain regions, not the propagation of aggregates from one region to another.
For a long time, brain processes that cause Alzheimer’s they were described with terms like ‘cascade’ and ‘chain reaction’. It is a difficult disease to study, as it develops over decades, and the definitive diagnosis can only be made after examining samples of brain tissue after death.
So far, research has relied heavily on animal models for study. The results obtained in mice suggested that the disease spread rapidly, because groups of toxic proteins colonized different parts of the brain.
“The idea was that Alzheimer’s developed in a similar way to many cancers, which means that clumps of toxic proteins formed in one region and spread throughout the brain,” says Meisl.
We found that when Alzheimer’s starts they already exist. [de proteínas tóxicas] in multiple regions of the brain, so trying to stop it from spreading between regions will do little to slow the disease.
Georg Meisl of Yusuf Hamied’s chemistry department in Cambridge and first author of the paper
Instead, he adds, “we found that when Alzheimer’s starts, there are already aggregates in various regions of the braintherefore, trying to prevent the spread between regions will do little to stop the disease. “
The authors also noted that replication of tau aggregates it’s surprisingly slow: it takes up to five years. “The neurons are very good at preventing these portal groups from forming, but we have to find ways to make them even better if we are to develop an effective treatment,” he says. David Klenerman, co-author of the study and member of the Dementia Research Institute of Cambridge. “It’s fascinating how biology has evolved to stop protein aggregation,” he emphasizes.
The value of working with human data
For Tuomas knowles, also from the Cambridge Chemistry department and co-author of the paper, “this research demonstrates the value of working with human data rather than with imperfect animal models”.
According to Knowles, the main finding of this work “is that interrupting the replication of aggregates rather than their propagation will be more effective in the stages of the disease we studied.”
The authors claim that their methodology could be used to aid in the development of treatments for Alzheimer’s, which affects about 44 million people worldwide, targeting the most important processes that occur when humans develop disease. In addition, this method can be applied to other neurodegenerative diseases, such as Parkinson’s, they point.
The methodology can be used to assist in the development of treatments and can also be applied to other neurodegenerative diseases.
In Georg Meisl’s opinion, his study “provides a new way to get more information about what happens in Alzheimer’s disease from patient data. This can allow us to discover what we should change with the medication to stop the disease, and predict how much we have to do to achieve a significant improvement in patients”.
Researchers plan to examine the first processes in the development of Alzheimer’s disease, and extending the studies to other diseases, such as frontal temporal dementia, hellohead trauma and progressive supranuclear palsy, in which tau aggregates also form during the disease.
Knowles believes that “it’s exciting to see the progress in this fieldFifteen years ago, we and other scientists determined the basic molecular mechanisms for simple systems in a test tube; but now we can study this process at the molecular level in real patients, which is an important step to develop treatments one day”, he concludes.
Reference:
georg meisl et al. “Determining steps of the in vivo rate of tau seed accumulation in Alzheimer’s disease”, Advances in Science (October 2021)
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