Non-invasive, in vivo monitoring of neuronal transport impairment in a mouse model of tauopathy using MEMRI

Anne Bertrand (1, 2, 3) , Umer Khan (4) , Dung M. Hoang (4) , Dmitry S. Novikov (4) , Pavan Krishnamurthy (4) , Hameetha B. Rajamohamed Sait (4) , Benjamin W. Little (4) , Einar M. Sigurdsson (4, 5) , Youssef Z. Wadghiri (4)

1 ARAMIS - Algorithms, models and methods for images and signals of the human brain = Algorithmes, modèles et méthodes pour les images et les signaux du cerveau humain [ICM Paris]
2 ICM - Institut du Cerveau et de la Moëlle Epinière = Brain and Spine Institute
3 CHU Pitié-Salpêtrière [AP-HP]
4 NYU - New York University School of Medicine
5 University of Iceland [Reykjavik]

The impairment of axonal transport by overexpression or hyperphosphorylation of tau is well documented for in vitro conditions; however, only a few studies on this phenomenon have been conducted in vivo, using invasive procedures, and with contradictory results. Here we used the non-invasive, Manganese-Enhanced Magnetic Resonance Imaging technique (MEMRI), to study for the first time a pure model of tauopathy, the JNPL3 transgenic mouse line, which overexpresses a mutated (P301L) form of the human tau protein. We show progressive impairment in neuronal transport as tauopathy advances. These findings are further supported by a significant correlation between the severity of the impairment in neuronal transport assessed by MEMRI, and the degree of abnormal tau assessed by histology. Unlike conventional techniques that focus on axonal transport measurement, MEMRI can provide a global analysis of neuronal transport, i.e. from dendrites to axons and at the macroscopic scale of fiber tracts. Neuronal transport impairment has been shown to be a key pathogenic process in Alzheimer’s disease and numerous other neurodegenerative disorders. Hence, MEMRI provides a promising set of functional biomarkers to be used during preclinical trials to facilitate the selection of new drugs aimed at restoring neuronal transport in neurodegenerative diseases.

Mots clés: Alzeheimer's disease; MEMRI; Axonal transport; Neuronal transport; Tauopathy

Domaines: Organes des sens

Anne Bertrand, Umer Khan, Dung M. Hoang, Dmitry S. Novikov, Pavan Krishnamurthy, et al.. Non-invasive, in vivo monitoring of neuronal transport impairment in a mouse model of tauopathy using MEMRI. NeuroImage, 2013, 64, pp.693 - 702. ⟨10.1016/j.neuroimage.2012.08.065⟩. ⟨hal-01439335⟩