Researchers identify new genetic risk factors for Alzheimer’s

Researchers in Europe, the US and Australia have identified 75 regions of the human genome that are associated with Alzheimer’s disease. 42 of these regions are novel, meaning that they have never before been implicated in the disease.

The findings, published in Nature Genetics, bring new knowledge of the biological mechanisms at play and open up new avenues for treatment and diagnosis.

As part of an international collaboration, researchers from Inserm, Institut Pasteur de Lille, Lille University Hospital and Université de Lille conducted a genome-wide association study (GWAS) on the largest Alzheimer’s patient group set up until now.

These studies consist of analysing the entire genome of tens of thousands or hundreds of thousands of individuals, whether healthy or sick, with the aim of identifying genetic risk factors associated with specific aspects of the disease.

Using this method, the scientists were able to identify 75 regions (loci) of the genome associated with Alzheimer’s, 42 of which had never previously been implicated in the disease. 

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

The scientists confirmed the importance of these pathological processes. Their analyses of the various genome regions confirm that some are implicated in amyloid peptide production and Tau protein function.

These analyses also reveal that a dysfunction of innate immunity and of the action of the microglia is at play in Alzheimer’s disease.

This study shows for the first time that the tumour necrosis factor alpha (TNF-alpha)-dependent signaling pathway is involved in disease.

These findings confirm the utility of the following: the conduct of clinical trials of therapies targeting the amyloid precursor protein, the continuation of microglial cell research that was initiated a few years ago, and the targeting of the TNF-alpha signalling pathway.

Photo by National Cancer Institute