title: Non-invasive, in vivo monitoring of neuronal transport impairment in a mouse model of tauopathy using MEMRI.
abstract: 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.
authors.affiliation: The Bernard & Irene Schwartz Center for Biomedical Imaging, Department of Radiology, New York University Langone Medical Center, New York, NY 10016, USA.
authors.forename: Anne
authors.initials: A
authors.lastname: Bertrand
authors.forename: Umer
authors.initials: U
authors.lastname: Khan
authors.forename: Dung M
authors.initials: DM
authors.lastname: Hoang
authors.forename: Dmitry S
authors.initials: DS
authors.lastname: Novikov
authors.forename: Pavan
authors.initials: P
authors.lastname: Krishnamurthy
authors.forename: Hameetha B
authors.initials: HB
authors.lastname: Rajamohamed Sait
authors.forename: Benjamin W
authors.initials: BW
authors.lastname: Little
authors.forename: Einar M
authors.initials: EM
authors.lastname: Sigurdsson
authors.forename: Youssef Z
authors.initials: YZ
authors.lastname: Wadghiri
mesh_terms: D000818:Animals; D002712:Chlorides / Q000493:pharmacokinetics*; D003287:Contrast Media / Q000493:pharmacokinetics; D006801:Humans; D008279:Magnetic Resonance Imaging / Q000379:methods*; D017895:Manganese Compounds / Q000493:pharmacokinetics*; D051379:Mice; D008822:Mice, Transgenic; D009410:Nerve Degeneration / Q000378:metabolism* / Q000473:pathology*; D009474:Neurons / Q000378:metabolism / Q000473:pathology; D009435:Synaptic Transmission; D024801:Tauopathies / Q000378:metabolism* / Q000473:pathology*; D016875:tau Proteins / Q000235:genetics
chemical_list: D002712:Chlorides; D003287:Contrast Media; D017895:Manganese Compounds; D016875:tau Proteins; C025340:manganese chloride