Alzheimer's Disease: Modelization, Biomarkers, Preclinical Imaging, Therapeutic Evaluations
UMR CEA CNRS 9199, MIRCen, 18 Route du Panorama, 92265 Fontenay aux Roses, France
Resp. Marc Dhenain

Cerebral aging is a public health issue in our societies. It is associated with the appearance of serious pathologies such as Alzheimer's disease. There is currently no cure for these diseases. This lack of treatment is partly related to (i) a poor understanding of the mechanisms associated with these pathologies (ii) the absence of predictive animal models of treatment efficacy (iii) the absence of relevant biomarkers to examine the effectiveness of new treatments in animal models.

Our research group focuses on three central themes to understand cerebral aging and developing therapies against age-related cognitive impairment such as Alzheimer's disease.

1) The characterization animal models to explore physiopathogenic mechanisms associated with age-related brain diseases and to test new therapies.

Our studies are based on transgenic mice that model Alzheimer's disease and on the mouse lemur primate, which is a model of neurodegenerative diseases linked to aging. This animal presents, as it ages, cognitive alterations, alterations of cerebral metabolism, cerebral atrophy and amyloid deposits.

One of our research themes concerns the detection of mechanisms associated with the appearance of cerebral pathologies in these animals and aims to understand these mechanisms by being able to reproduce them. In particular, we are working on the "prion" hypothesis of Alzheimer's disease and have demonstrated that it is possible to induce Alzheimer pathology by inoculation of contaminated tissues.

2) The evaluation of new biomarkers of pathological cerebral aging.

We focus in particular on new in vivo microscopic, anatomical and functional biomarkers of pathological cerebral aging. For example, one of our researches focuses on in vivo imaging of amyloid plaques and neurofibrillary degeneration by magnetic resonance imaging (MRI). These lesions are central lesions to the physiopathogenic mechanisms of Alzheimer's disease. More specifically, we have developed Gadolinium staining method which allows the detection of amyloid plaques in vivo. We also developed new markers based on the use of llama antibodies. In addition, we also use markers of cerebral pathologies based on brain metabolism, characterization of neural networks, white matter fibers or markers of neuronal health.

3) The animal models and innovative biomarkers that we develop are used to evaluate new therapies against cerebral aging and Alzheimer's disease.

In particular, we worked on treatments that modulate amyloid load, neurotrophic factors or neuroprotective agents. Some of the treatments we evaluated are tested in clinical phases in humans.