Alzheimer’s: 75 new genetic risk factors associated with the disease

A large-scale study

75 regions of the genome associated with the disease

These studies consisted of analyzing the entire genome of all these individuals, to identify genetic risk factors associated with specific traits of the disease. Result: the researchers identified 75 regions of the genome associated with Alzheimer’s disease, including 42 new ones that had not previously been implicated in the disease.

“After this important discovery, the rest of our work consisted in 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 therefore better understand the cellular mechanisms and pathological processes at artwork”underlines Jean-Charles Lambert, main coordinator of this study published in the journal Nature Genetics on April 4.

Two phenomena confirmed in the disease

Thanks to their work, the scientists were able to confirm the two pathological phenomena known to scientists in the disease: the accumulation of beta-amyloid peptides and the modification of the Tau protein, which is found in the form of aggregates in neurons. .

According to Jean-Charles Lambert, “these results confirm and reinforce our knowledge of the pathological processes involved in the disease, and open up new avenues for therapeutic research. They confirm, for example, the interest of conducting clinical trials on treatments targeting the amyloid precursor protein..

Other elements, such as a dysfunction of innate immunity and the action of cerebral microglia, which serves to eliminate toxic substances from the brain, are also highlighted by this work.

Towards a disease assessment score?

Along with their findings, the authors also set up a “genetic risk score” that better assesses people who will eventually develop Alzheimer’s disease, within three years of the onset of clinical disorders.

“This tool is not at all intended for clinical practice at the moment, but it could be very useful in setting up therapeutic trials to categorize participants according to their risk and better assess the interest of the drugs tested. says Jean-Charles Lambert.

Better understand Alzheimer’s

Alzheimer’s disease affects more than a million people in France, it generally appears after the age of 65 and is the most common form of dementia. Scientists know that there is a strong predominance of genetic risk. It is also a complex multifactorial pathology. For the majority of cases, it would be caused by the interaction between a genetic predisposition coupled with environmental factors.

There is currently no treatment for this disease. The only drugs available slow down cognitive decline and reduce the disorders present in those affected. The research team therefore wishes to continue its work with a view to advancing its results.