Alzheimer’s disease affects between 855,000 and 1,000 ,000 persons in France today; it is estimated that there are more than 225,000 new cases each year. Nearly one and half million people might be affected by 2020.
Dozens of drugs are in development to treat this serious neurodegenerative disease. Despite these efforts, no effective treatment has been discovered to date. The most innovative and promising therapies have not had significant impact on the course of the disease. In the opinion of international experts, even the treatment of reference (by acetylcholinesterase inhibitors) is only of limited benefit to patients.
There are three reasons for this. First is the lack of real understanding of the mechanisms of the disease, namely alterations in the behaviour of brain neurons. Secondly, by the time the disease is diagnosed, it has already seriously affected the brain. Finally, there are probably several subgroups of the disease; a particular drug might be effective on one of these subgroups but not on others.
The situation would probably be different if one could intervene earlier, at a time when the brain can still compensate for the effects of the disease and has a sufficient «functional reserve», and distinguish between the different forms of the disease.
The Institut du Cerveau – ICM’s response
The team of Pr Charles Duyckaerts and Dr Stéphane Haïk seeks to understand the mechanisms leading to Alzheimer’s disease with two main approaches:
The importance of environmental factors, especially the metabolism of cholesterol in the development of this disease is known. One of the major preventive factors (except intellectual and physical activity) is regular consumption of omega3 lipids. By understanding the role of cholesterol metabolism in the disease, it should be possible to find new avenues for a cure.
In parallel to his research on the «path» of cholesterol, Doctor Haïk is interested in the prion proteins. These proteins, like viruses, are able to contaminate the others and trigger a cascade of modifications which change the protein’s configuration leading to aggregation and toxicity. Recent work shows that this phenomenon occurs for one of the two major proteins in Alzheimer’s disease.
Understanding how a useful protein is changed into a toxic protein which then contaminates the others may suggest ways to counteract this harmful mechanism.
Moreover, the success in the fight against this scourge starts with the ability to make and earlier and pore precise diagnosis. Pr Bruno Dubois and his team showed, in 2007, that it was possible to detect the onset of clinical signs* of Alzheimer’s 3 years before they occur. Two key elements for this early diagnosis of the disease are: the detection of very specific memory disorders (of the «hippocampal» type) and a change in the concentration of certain proteins in the cerebrospinal fluid. This work was made possible thanks to the large cohorts of patients available for study.
* Stereotypical behaviour, inappropriate comportment, loss of interest, reduction of personal care, language disorders, characterized by a deficit of verbal fluency and naming (source: INSERM)