75 genetic risk factors have been identified

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[EN VIDÉO] Soon a blood test to detect Alzheimer’s disease?
Soon it would be possible to perform a blood test for Alzheimer’s disease that could be done in your doctor’s office.

The identification of risk factor’s genetics of Alzheimer disease is a crucial research topic to better understand the pathology and handle it better. The progress of the analysis of the genome human, along with the implementation of large pan-genomic association studies; These studies consist of analyzing the complete genome of thousands, or even tens of thousands of individuals, healthy or sick, to identify risk factors. genetic associated with specific features of the disease, today allow important advances in the field.

Alzheimer’s disease is the most common of dementias, which affects approximately 1,200,000 people in France. It is a complex multifactorial pathology, which generally appears after the age of 65 and for which there is a strong genetic component. Most cases would be caused by the interaction of different factors from predispositions genetics with environmental factors.

If the disease is increasingly better understood, there is currently no treatment to cure it. Available medications are primarily intended to slow cognitive decline and reduce certain behavioral problems. One of the great challenges of research is to better characterize the genetic risk factors of the disease, better understand its origins by identifying the pathophysiological processes involved (all the functional problems caused by a disease or a certain condition), and thus propose new therapeutic targets.

As part of an international collaboration, and under the coordination of Inserm Research Director Jean-Charles Lambert, researchers from Inserm, the Institut Pasteur de Lille, the University Hospital of Lille and the University of Lille conducted A study genome-wide association Genome-wide association studyGWAS) in the largest group of Alzheimer’s patients ever created: Researchers analyzed genetic data from 111,326 people who received a diagnosis Alzheimer’s disease or having relatives affected by the disease and 677,663 healthy “controls”. This data comes from several large Historiquement, une légion romaine comptait dix cohortes numérotées de I à X. © Peter Bernik, Shutterstock
Étude de cohorte
Une étude de…” data-image=”https://cdn.futura-sciences.com/buildsv6/images/midioriginal/9/e/4/9e4667b473_98839_cohorte.jpg” data-url=”https://news.google.com/sante/definitions/medecine-cohorte-15863/” data-more=”Lire la suite”>cohorts
European countries grouped in the consortium European Alzheimer and Dementia Biobank (EADB).

Encouraged by advances in the analysis of genomeThese studies consist of analyzing the entire genome of tens of thousands, or even hundreds of thousands of individuals, healthy or diseased, to identify genetic risk factors associated with specific features of the disease.

Using this method, the scientists were able to identify 75 regions of the genome (called loci) associated with Alzheimer’s, 42 of which had not previously been implicated in this disease. ” After this important discovery, the rest of our work consisted of characterizing these regions of the genome that we had identified in order to give them meaning in relation to our biological and clinical knowledge, and thus better understand cellular mechanisms and processes. pathological at work “, emphasizes Jean-Charles Lambert.

Highlighting pathological phenomena.

Two pathological brain phenomena are already well documented in Alzheimer’s disease: the accumulation of On parle de dipeptides, de tripeptides lorsque…” data-url=”https://news.google.com/sante/definitions/biologie-peptide-292/” data-more=”Lire la suite”>peptides beta-amyloid and modification of Tau, a Rôles des protéines
Les protéines peuvent assurer des fonctions très diverses au sein de la cellule ou de l’organisme. 
Elles peuvent avoir :
un rôle structural (comme l’actine ou la tubuline qui…” data-image=”https://cdn.futura-sciences.com/buildsv6/images/midioriginal/4/6/e/46e94f9da7_50034188_actine-thomas-splettstoesser-cc.jpg” data-url=”https://news.google.com/sante/definitions/biologie-proteine-237/” data-more=”Lire la suite”>protein
found as aggregates in neurons.

Scientists here have confirmed the importance of these pathological processes. In fact, their analyzes of the different regions of the genome confirm that some are involved in the production of amyloid peptides and in the functioning of tau protein.

In addition, these analyzes also reveal that a dysfunction of immunity innate and the action of Elles correspondent à un type de cellule gliale, au même titre que les cellules macrogliales.
Elles possèdent une forme en étoile, sont de…” data-image=”https://cdn.futura-sciences.com/buildsv6/images/midioriginal/2/2/d/22d24717c0_50035177_microglie-cellule-etoile-grzegor-wicher.jpg” data-url=”https://news.google.com/sante/definitions/biologie-microglie-6197/” data-more=”Lire la suite”>microglie
(immune cell present in the Rôle et fonction du système nerveux central
Le…” data-image=”https://cdn.futura-sciences.com/buildsv6/images/midioriginal/c/2/d/c2d8e160dd_81478_cerveau-pose.jpg” data-url=”https://news.google.com/sante/definitions/corps-humain-systeme-nerveux-central-15268/” data-more=”Lire la suite”>Central Nervous System
which acts as a “garbage collector” by removing toxic substances) is at work in Alzheimer’s disease.

Finally, this study demonstrates for the first time the involvement of the tumor necrosis factor-alpha (TNF-alpha)-dependent signaling pathway in disease — tumor necrosis factor-alpha is a cytokineprotein immune system involved in the trickinflammationparticularly in the mechanisms of tissue injury.

These results confirm and reinforce our knowledge of the pathological processes involved in the disease, and open new avenues for therapeutic research. They confirm, for example, the value of conducting clinical trials on treatments aimed at amyloid precursor proteinto continue the work on microglial cells, started a few years ago, but also to target the TNF-alpha signaling pathway.

The utility of the genetic risk score

Based on their findings, the researchers also constructed a genetic risk score that helps better assess who among people with cognitive disorders, will progress to Alzheimer’s disease, within three years after the clinical manifestation of the disorders. ” Currently, this tool is not intended for clinical practice, but it could be very useful for establishing therapeutic trials to categorize participants according to their risk and better assess the benefit of the drugs tested. » explains Jean-Charles Lambert.

The team now wishes to continue their work in an even larger group to validate and scale up their results. Beyond this exhaustive characterization of the genetic factors of Alzheimer’s disease, the team is also developing many approaches from Cell Biology and molecular to determine its role in the development of the disease.

In addition, given that at the moment genetic research has been carried out mainly in populations of Caucasian origin, one of the future challenges will be to carry out the same type of study in other groups to determine if the risk factors are the same from one population to another. . another, which would reinforce its importance in the pathophysiological process.

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