Nicolas Villain

Very early on, I embarked on a dual medical-scientific pathway through the Inserm-Liliane Bettencourt school, where I specialised in Alzheimer's disease, in particular through the multimodal study of neuroimaging biomarkers of the disease at the end of the 2000s in Caen, in Dr Gaël Chételat's team. I then continued my medical training and completed a neurology internship and clinic in Paris, at the Institut de la Mémoire et de la Maladie d'Alzheimer at Pitié-Salpêtrière hospital, directed by Professor Bruno Dubois, while carrying out research projects relating to the neuroimaging of Alzheimer's disease at the same time.

More recently, to keep up with the rise in fluid biomarkers, I trained in the spectrometric analysis of human fluids (such as cerebrospinal fluid and plasma) at the Innovations in Mass Spectrometry for Health Laboratory run by Dr François Fenaille at CEA Saclay. When the opportunity arose to launch a research team at the Institut du Cerveau focusing on the study of fluid biomarkers of Alzheimer's disease under the leadership of Professor Kaj Blennow, a world authority on the subject, it fitted in perfectly with my medical and scientific training as well as my scientific projects: joining the project was a no-brainer.

The project has a dual objective. Firstly a clinical dimension consisting of developing new fluid biomarkers for Alzheimer's disease and then testing their diagnostic and prognostic value in the patient cohorts at our disposal. Then a more fundamental mechanistic dimension which aims to understand the links between biomarkers and the biological mechanisms of the disease through studies with mouse models.

Kaj Blennow is both the pioneer and world leader in research into fluid biomarkers of Alzheimer's disease. He now has 3,026 publications cited 152,889 times, with a remarkable h-index of 179. In the 1990s, he developed the first immunoassays for tau and ABeta proteins in cerebrospinal fluid, and today continues to be the world leader in the development of new methods. He has the leadership, the knowledge and the scientific and managerial experience needed to bring this project to fruition, and the connections with the manufacturers involved in these developments. His time is precious, but his impact is crucial. The next steps are to demonstrate our ability to bring this project to a successful conclusion and then to sustain it over the longer term, in an extremely dynamic global medical-scientific environment.

The advent of second-generation immunoassay and high-resolution mass spectrometry techniques has recently made it possible to measure biomarkers of Alzheimer's disease in more easily accessible human fluids such as plasma, whereas until now they were only available in cerebrospinal fluid via lumbar puncture. The biomarkers currently validated are completing their final stages before they can be used in routine clinical practice. What sets our team apart is its desire to work closely with clinical prognostic objectives: the biomarkers currently identified are excellent for identifying the cerebral lesions of Alzheimer's disease, which are unfortunately very common in the general population after the age of 60.

Our ambition is to develop biomarkers that will enable us to establish a reliable prognosis of the risk of subsequent decline in asymptomatic individuals with lesions of the disease. This characterisation of the prognosis is vital in order to better target the individuals most likely to benefit from such treatments at a time when preventive trials using risky and complex therapies are beginning to emerge. Understanding the significance of these biomarkers in the biological cascade responsible for the disease is also vital, particularly with the arrival of new therapies. Our second objective is therefore to improve our knowledge of the links between the mechanisms of the disease and these biomarkers, in order to better identify the mechanisms of the disease in vivo and develop personalised medicine for Alzheimer's disease.

Above all, my sincere gratitude. Alzheimer's disease is a major public health problem, recognised by everyone, which unfortunately affects each and every one of us to the first or second degree. Its importance continues to grow, in an unflattering comparison with the therapeutic progress made in cancer and cardiovascular disease. We are delighted that the AXA Research Fund has also identified it as one of its priorities.
Worldwide research into Alzheimer's disease is advancing thanks partly to the involvement of sponsors such as the AXA Research Fund, which is helping to keep France in the race against this disease and to highlight its unique features, such as the excellence of its training and the originality of its solutions, for the benefit of patients. This originality is vital because we are dealing with a complex disease that we still don’t completely understand. Corporate sponsorship is playing an increasingly important role in the progress of research into this disease, following the example of the United States, where substantial funding from private foundations is enabling original and ambitious research programmes to be launched. It is this ambition and originality in the service of patients and their families that we also wish to put in place with this program.