Résumés disponibles (92) :

ALBERT Marie (INSERM U1172 éq. 01 - Morvane COLIN)
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@mail :  marie.albert@inserm.fr      tél. :  0635554279


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Titre de la communication :
Passive immunotherapeutic approaches to interfere with the spreading of Tauopathies
Auteurs (et leurs adresses) de la communication :
1Marie ALBERT, 1Raphaelle Caillierez, 1Séverine Begard, 2Jean-Philippe Courade, 2Martin Citron, 1Luc Buée and 1Morvane Colin 1 Univ. Lille, Inserm, CHU Lille, UMR-S 1172 - JPArc 2 UCB Biopharma Sprl, Braine-l\'Alleud ,Belgium
Résumé de la communication :
Tauopathies are neurodegenerative diseases characterized by the intracellular accumulation of pathological Tau species. In Alzheimer\'s disease (AD), neurofibrillary degeneration progresses in a hierarchical pathway that might be explained by an intercellular transmission of pathological Tau species acting as “Prion-like” proteins. In this context, extracellular Tau-blocking agents are relevant to interfere with the spreading of tauopathies. Consequently, we developed in vitro and in vivo models of tauopathy to test anti-Tau-antibodies that may interfere with the spreading of Tau pathology.
Tau species were generated using either lentiviral vectors or human brain materials purified from AD patients. In collaboration with UCB Pharma, antibodies recognizing pathological Tau and isotype controls were tested. In vitro, Tau transfer was followed in microfluidic chambers by immuno-fluorescence with or without antibodies to select the best blocking agents. A seeding model of tauopathy has been developed in vivo by intracranial injection of AD brain homegenates in young Tau transgenic mice (ThyTau30). These latter were then treated by weekly intra-peritoneal injection of antibodies for one month. Tau pathology was analysed by immunohistochemistry with the anti-Tau antibodies: AT8 (hyperphosphorylated Tau) and AT100 (insoluble Tau).
In vitro, in microfluidics devices, we set up a model of interneuronal transfer of Tau and as a proof of concept we observed that commercially available anti-V5 antibodies are able to reduce the intercellular transfer of Tau-V5. In vivo, AT8 and AT100 immunoreactivities were much stronger in seeded THY-Tau30 mice than in control. Differential effects were observed among antibodies: some have demonstrated a blocking effect.
In conclusion, brain materials purified from AD patients contain seeds that are able to mediate a robust and rapid model of Tau seeding in ThyTau30 mice. Further experiments at larger scales are now on going to obtain more significant results concerning the blocking effect of anti-Tau antibodies. In parallel to select the best blocking agents, we have to develop a robust and quantitative technique to accurately measure Tau transfer in microfluidic devices.

ALBERT Marie (INSERM U1172 éq. 01 - Morvane COLIN)