“Although it is known that Alzheimer’s disease can start up to 20 years before the first symptoms appear, the lack of knowledge about how it progresses prevents the development of effective treatments, as well as a clear diagnosis to confront this neurodegenerative disease, which origin is also unknown.” This is pointed out by the researcher at the UMA David Baglietto, specializing in the study of risk factors –namely, genetic, environmental and lifestyle– influencing on the onset and progression of this pathology.

In searching for a possible therapeutic target to stop the progress of this disease, an international scientific team, led by researchers at the Department of Cell Biology, Genetics and Physiology of the UMA and also members of the ‘BagliettoLab’ and the NeuroAD research group, has identified different factors involved in the propagation processes.

To this end, they have compared cortical brain samples from Alzheimer’s disease patients –provided by the University of Irvine (California)– to samples from transgenic models, showing that the disease progresses differently in both cases, since cells do not behave in the same way in each model. The results of this research have been recently published in the scientific journal Aging Cell.

In this respect, Baglietto explains that, for example, the immune response is different, as is the appearance of synaptic damage or the way in which Alzheimer’s disease exarcebates. “This finding sheds light on the fact that a lot of medication that works successfully in preclinical models does not do so in humans afterward,” he clarifies.

Toxic aggregates in the brain

According to the researcher at the Faculty of Science of the UMA, one of the fundamental characteristics of this disease is the significant accumulation of toxic protein aggregates in the patients’ brain. “These brain accumulations are formed as a consequence of an abnormal folding of soluble proteins, which can occur due to multiple causes that are not yet known and following different pathogenic mechanisms,” he clarifies.

The scientist points out that, once initiated, such abnormal conformations are able to propagate and induce these same aberrant foldings into other soluble proteins, spreading the disease to different brain regions. “For that reason, it is extremely important to know which are the most pathogenic protein isoforms or foldings and determine how the propagation occurs”.

Thanks to this study, it has been found that the samples of Alzheimer’s disease patients contain pathogenic isoforms of beta-amyloid peptide that further boost the formation of senile plaques –the toxic protein aggregates– in comparison with the animal models of the disease that were used for this research.

An international multidisciplinary team

This research has been coordinated by the UMA for the last four years, led by David Baglietto, based on the work of the PhD candidate of the Cell Biology Area Juana Andreo. It has been also conducted with the collaboration of scientists at the University of California and Texas (United States) and the Institute of Crystallography of Catania (Italy). In addition, among its 21 authors are the IBIMA-BIONAND Platform, the Neurodegenerative Disease Center CIBERNED or the Integrative Center of Biology and Applied Chemistry of the Bernardo O’Higgins University (Chile).

The specialists involved say that these studies are “very important”, since a greater knowledge of the factors, cell types and protein isoforms responsible for boosting aggregative processes can be an “excellent” therapeutic target to slow down or stop the pathogenic progress of Alzheimer’s disease, achieving a treatment capable of modifying its progress, a treatment which “has not yet been achieved successfully”.

As next steps, the University of Malaga points to improving the models that reproduce the disease, as well as to ‘humanize’ certain genes to be able to reproduce it better.