Alzheimer's disease: researchers on the trail of microbes

Alzheimer’s disease continues to challenge scientists and physicians. How is it triggered? Why does it progress rapidly in some patients and not in others? There are still no clear answers to these questions. Certainly, it is commonly accepted that this pathology is characterized by an abnormal accumulation of proteins in the brain – amyloid beta peptides around neurons (the famous “senile plaques”) and Tau proteins inside these nerve cells. But it happens that people have significant concentrations of these clusters without having memory problems, or vice versa. Other factors therefore come into play. Among the potential culprits, researchers suspect the involvement of very widespread microbes, such as herpes, toxoplasmosis or the Epstein-Barr virus, responsible for mononucleosis.

“Studies have already shown a correlation between a positive serology for one of these pathogens, a sign of exposure of our body to these microbes, and the fact of developing the disease or not”, indicates Elsa Suberbielle, in charge of research at the CNRS and the Toulouse Institute of Infectious and Inflammatory Diseases (Infinity). But here again, not all infected people – 50% of the population for toxoplasmosis, 80% for herpes viruses – fall ill. An accomplice would therefore be at work: our immune system. “These microbes settle latently in the body. We believe that this can sometimes cause changes in immunity, which would then no longer play its role correctly in the “cleaning” of amyloid and tau proteins”, details the specialist.

Complex interactions between our genetic heritage, our immunity and microbes

This research is all the more promising as the latest discoveries in genetics point to the role of mutations in certain genes regulating immunity in predisposition to Alzheimer’s disease. “However, everything is not written in advance: monozygotic twins, with the identical genome, will not necessarily have the same immune profile, because they will not have been exposed to the same infections”, notes Elsa Suberbielle. Alzheimer’s disease would then arise from the complex interactions between the environment and our genes.

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A recent advance has come to support this hypothesis: scientists have discovered a correlation between the cognition index of patients and the presence in their brain of a certain type of white blood cells, T lymphocytes specifically directed against the mononucleosis virus. Absent cells in non-sick people… These are similar clues that the Toulouse team, with the support of the Foundation for Medical Research (1), would like to uncover for toxoplasmosis and herpes. For this, these scientists will analyze the blood of 300 patients and compare it to that of healthy subjects, in search of specific “immune signatures”.

Prevent infections to prevent disease?

“The new immunology tools provide us with very detailed information on the molecules that make up our immunity, their state of activation, their specificities, their action… By combining these data, we hope to identify a particular profile linked to Alzheimer’s” , explains Elsa Suberbielle. Work completed in the laboratory, on models of the disease infested by the toxoplasmosis parasite: “Our first results are encouraging, because as we thought, these models trigger the disease earlier”.

Ultimately, these leads could lead to specific biomarkers of Alzheimer’s. A simple blood test would then be enough to allow doctors to know which patients are at risk of seeing their condition deteriorate rapidly. Perhaps it will even be possible to modify the immune system of people at risk, to block the pathological process. And if certain microbes do indeed have an effect on the course of the disease, it would then be possible to take measures upstream to prevent both infections and this dreaded memory degradation.

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(1) The Foundation for Medical Research (FRM) is the leading private funder of research on Alzheimer’s disease, with 33 projects funded to the tune of 9 million euros over the past five years. Every year, on the occasion of the World Day against this disease, the FRM conducts a campaign to mobilize and appeal for donations.