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Mudher et al. Acta Neuropathologica Communications (2017) five:99 DOI 10.1186/s40478-017-0488-REVIEWOpen AccessWhat will be the proof that tau pathology spreads by means of prion-like propagationAmrit Mudher1*, Morvane Colin2, Simon Dujardin3, Miguel Medina4, Ilse Dewachter5, Seyedeh Maryam Alavi Naini6, Eva-Maria Mandelkow7,8,9, Eckhard Mandelkow7,eight,9, Luc Bu two, Michel Goedert10 and PLA2G1B Protein HEK 293 Jean-Pierre Brion11*Abstract: Emerging experimental proof suggests that the spread of tau pathology in the brain in Tauopathies reflects the propagation of abnormal tau species along neuroanatomically connected brain regions. This propagation could take place by means of a “prion-like” mechanism involving transfer of abnormal tau seeds from a “donor cell” to a “recipient cell” and recruitment of typical tau in the latter to generate new tau seeds. This assessment critically appraises the evidence that the spread of tau pathology occurs via such a “prion-like” mechanism and proposes quite a few suggestions for directing future research. Suggestions for definitions of regularly applied terms in the tau field are presented in an attempt to clarify and standardize interpretation of study findings. Molecular and cellular factors affecting tau aggregation are briefly reviewed, as are possible contributions of physiological and pathological post-translational modifications of tau. Furthermore, the experimental evidence for tau seeding and “prion-like” propagation of tau aggregation which has emerged from cellular assays and in vivo models is discussed. Propagation of tau pathology applying “prion-like” mechanisms is anticipated to incorporate numerous actions which includes cellular uptake, templated seeding, secretion and intercellular transfer through synaptic and non-synaptic pathways. The experimental findings supporting each and every of these measures are reviewed. The clinical validity of these experimental findings is then debated by contemplating the supportive or contradictory findings from patient samples. Additional, the part of physiological tau release within this scenario is examined because emerging data shows that tau is secreted but the physiological function (if any) of this secretion in the context of propagation of pathological tau seeds is unclear. Bona fide Prolactin/PRL Pig prions exhibit precise properties, like transmission from cell to cell, tissue to tissue and organism to organism. The propagation of tau pathology has so far not been shown to exhibit all of those actions and how this influences the debate of irrespective of whether or not abnormal tau species can propagate within a “prion-like” manner is discussed. The exact nature of tau seeds responsible for propagation of tau pathology in human tauopathies remains controversial; it might be tightly linked for the existence of tau strains stably propagating peculiar patterns of neuropathological lesions, corresponding towards the different patterns noticed in human tauopathies. That this really is a property shared by all seed-competent tau conformers is not however firmly established. Further investigation is also needed to clarify the partnership between propagation of tau aggregates and tau-induced toxicity. Genetic variants identified as risks things for tauopathies may possibly play a role in propagation of tau pathology, but a lot of extra studies are necessary to document this. The contribution of selective vulnerability of neuronal.