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First longitudinal study of an anti-Alzheimer immunotherapy by microscopic MRI


The group of Marc Dhenain (MIRCen) has developed an MRI microscopy technique that can track in vivo the fate of amyloid plaques. This technique was used to characterize an immunotherapy targeting specific forms of amyloid (called protofibrillar). The article, published in collaboration with Sanofi, demonstrates an effective partnership between the CEA and industrial partners. 

Published on 6 June 2016

Alzheimer's disease is characterized by microscopic lesions called "amyloid plaques". They appear up to 20 years before the clinical signs of the disease. Anti-amyloid immunotherapies are therapies that aim to mobilize the immune system to fight against these lesions. How to determine the effectiveness of these new treatments?

The group of Marc Dhenain (Multimodal Imaging of Neurodegenerative Diseases and Therapies, MIRCen) has developed an MRI microscopy technique that can track in vivo the fate of amyloid plaques. This technique was used to characterize an immunotherapy targeting specific forms of amyloid (called protofibrillar). The results of this study were published in March 2016 in the journal Frontiers in Aging Neuroscience. This is the first article presenting an MRI method allowing to follow the fate of individual amyloid plaques over time. It demonstrated that amyloid plaques are extremely stable lesions that never disappear spontaneously. MRI scans revealed​ that the tested therapy prevents the formation of amyloid plaques and helped to better characterize the mechanisms of action of this therapy. The article, published in collaboration with Sanofi, demonstrates an effective partnership between the CEA and industrial partners. It follows previous studies where the group of Marc Dhenain characterized the lack of toxicity of this therapy and where Thierry Delzescaux, another researcher of the team, revealed the beneficial effects of this immunotherapy with innovative 3D histology markers (published in April 2016 in Scientific Reports). Since the end of the study, the tested immunotherapy has been passed in clinical study in humans. The developed MRI method continues to be improved in order to be tested in animals and humans.


Longitudinal follow-up of amyloid plaques by MR imaging in mouse models of amyloidosis. The same mouse was imaged twice at three-month intervals and MR images from the same animals were registered. Hypointense spots corresponding to amyloid plaques were visible in the images. The plaques detected at the initial time point were still visible three months later (yellow arrows). Some new plaques occurred between the two time points (red arrows). Some plaques that were slightly visible at T0 and which were more visible three months later are labeled with pale yellow arrows.

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