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Mudher et al. Acta Neuropathologica Communications (2017) 5:99 DOI ten.1186/s40478-017-0488-REVIEWOpen AccessWhat is definitely 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 Jean-Pierre Brion11*Abstract: Emerging experimental evidence suggests that the spread of tau pathology inside the brain in Tauopathies reflects the propagation of abnormal tau species along neuroanatomically connected brain areas. This propagation could occur through a “prion-like” mechanism involving transfer of abnormal tau seeds from a “donor cell” to a “recipient cell” and recruitment of regular tau inside the latter to create new tau seeds. This review critically appraises the evidence that the spread of tau pathology occurs by means of such a “prion-like” mechanism and proposes several suggestions for directing future study. Suggestions for definitions of frequently employed terms within the tau field are presented in an attempt to clarify and standardize interpretation of investigation findings. Molecular and cellular things affecting tau aggregation are briefly reviewed, as are prospective contributions of physiological and pathological post-translational modifications of tau. On top of that, the experimental proof 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 employing “prion-like” mechanisms is anticipated to incorporate a number of methods such as cellular uptake, templated seeding, secretion and intercellular transfer by way of synaptic and non-synaptic pathways. The experimental findings supporting every single of those methods are reviewed. The clinical Recombinant?Proteins Siglec-9 Protein validity of these experimental findings is then debated by thinking of the supportive or contradictory findings from patient samples. Further, the role of physiological tau release in this situation is examined simply because emerging information shows that tau is secreted however the physiological function (if any) of this secretion in the context of propagation of pathological tau seeds is unclear. Bona fide prions exhibit particular 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 measures and how this influences the debate of regardless of whether or not abnormal tau species can propagate within a “prion-like” manner is discussed. The exact nature of tau seeds accountable for propagation of tau pathology in human tauopathies remains controversial; it could possibly be tightly linked towards the existence of tau strains stably propagating peculiar patterns of neuropathological lesions, corresponding for the diverse patterns observed in human tauopathies. That this is a house shared by all seed-competent tau conformers will not be but firmly established. Further investigation is also necessary to clarify the connection among propagation of tau aggregates and tau-induced toxicity. Genetic variants identified as dangers aspects for tauopathies could play a part in propagation of tau pathology, but many a lot more studies are required to document this. The contribution of selective vulnerability of neuronal.