found 75 regions of the genome related to the disease

by time news

R. Ibarra

Madrid

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A study published in the journal “Nature Genetics” has made it possible to identify 75 regions of the genome that are associated with Alzheimer’s disease. Forty two of these regions are new, meaning they have never been implicated in the disease before. The findings provide new insights into the biological mechanisms involved in this disease and open new avenues for its treatment and diagnosis.

The research has been carried out by the European Alzheimer’s & Dementia Biobank (EADB), a consortium in which Spanish centers such as the Ace Alzheimer Center Barcelona and the CIEN Foundation (Center for Neurological Disease Research) participate.

Alzheimer’s disease is the most common form of dementia and affects around 800,000 people in Spain.

This complex multifactorial disease, which usually develops after the age of 65, has a strong genetic component. Most cases are believed to be caused by the interaction of different genetic predisposing factors with environmental factors.

Therefore, the identification of genetic risk factors for Alzheimer’s disease is essential if we want to improve our understanding and treatment of it. Advances in the analysis of the human genome, along with genome-wide association studies, are now leading to major advances in this field.

But the truth is that today there is no cure. The available medications they are primarily intended to slow cognitive decline and reduce certain behavioral disorders.

To better understand the origins of the disease, one of the main research challenges is to better characterize its genetic risk factors by identifying pathophysiological processes at stake, and thus propose new therapeutic targets.

As part of this international collaboration, researchers from Inserm, the Pasteur Institute of Lille, the University Hospital of Lille and the University of Lille, all of them in France, carried out an association study of complete genome (GWAS) in the largest group of patients with Alzheimer’s created to date, under the coordination of the research director of the InsermJean-Charles Lambert.

Driven by advances in genome analysis, these studies consist of analyzing the entire genome of tens of thousands or hundreds of thousands of individuals, healthy or sick, with the aim of identifying genetic risk factors associated with specific aspects of the disease.

Agustín Ruiz, scientific director of the Ace Alzheimer Center Barcelona and current coordinator of the Spanish Dementia Genetics Consortium (DEGESCO), explains that “we are in a new era of research: genetics is going to allow us to get closer to the disease in order to find new therapeutic targets and advance in the design of personalized treatments».

Advances in the analysis of the human genome, along with genome-wide association studies, are now leading to major advances in this field.

Using this method, the scientists were able to identify 75 regions (loci) of the genome associated with Alzheimer’s, 42 of which had never before been implicated in the disease. “Following this discovery, we characterized these regions to give them meaning in relation to our clinical and biological knowledge, and thus gain a better understanding of the cellular mechanisms and pathological processes at play,” explains Lambert.

In Alzheimer’s disease, two pathological brain phenomena are already well documented: the accumulation of beta-amyloid peptides and the modification of the Tau proteinwhose aggregates are found in neurons.

This study confirms the importance of these pathological processes. His analyzes of the various regions of the genome confirm that some are involved in amyloid peptide production and Tau protein function.

Furthermore, these analyzes also reveal that in Alzheimer’s disease a dysfunction of innate immunity and the action of microglia (immune cells present in the central nervous system that play a “garbage collector” role by removing toxic substances).

Finally, this work shows for the first time that the signaling pathway dependent tumor necrosis factor alpha (TNF-alpha) is involved in the disease.

These findings confirm and expand our knowledge of the pathological processes involved in the disease and open new avenues for therapeutic research. For example, they confirm the usefulness of conducting clinical trials of therapies targeting amyloid precursor proteinthe continuation of research on microglial cells that began a few years ago and on the TNF-alpha signaling pathway.

Could be very useful when establishing therapeutic trials to classify participants according to their risk and improve the evaluation of the drugs being tested

Based on their findings, the researchers also designed a genetic risk score to better assess which patients with cognitive impairment, within three years of its clinical manifestation, will develop Alzheimer’s disease. “While this tool is not designed for use in clinical practice at present, could be very helpful by establishing therapeutic trials to classify participants according to their risk and improve the evaluation of the drugs that are tested,” he explains. Lambert.

For Pascual Sánchez Juan, scientific director of the CIEN Foundation, the work “represents an important step not only in understanding the causes of the disease, but also in the use of this information in the clinic and towards the establishment of precision medicine.” ».

And adds the scientific director of the CIEN Foundation that “genetic risk scoring systems and new advances in blood markers and ‘digital markers’ will be a turning point in the diagnosis and treatment of these diseases, allowing greater precision and precociousness when starting therapeutic interventions”.

Also, since genetic research has been done primarily in Caucasian populations, one of the considerations for the future will be to conduct the same type of studies in other groups to determine whether risk factors are the same between different populations.

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