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%0 Journal Article %T Novel self-replicating α-synuclein polymorphs that escape ThT monitoring can spontaneously emerge and acutely spread in neurons %V 6 %N 40 %P eabc4364 %U https://advances.sciencemag.org/lookup/doi/10.1126/sciadv.abc4364 %X The conformational strain diversity characterizing α-synuclein (α-syn) amyloid fibrils is thought to determine the different clinical presentations of neurodegenerative diseases underpinned by a synucleinopathy. Experimentally, various α-syn fibril polymorphs have been obtained from distinct fibrillization conditions by altering the medium constituents and were selected by amyloid monitoring using the probe thioflavin T (ThT). We report that, concurrent with classical ThT-positive products, fibrillization in saline also gives rise to polymorphs invisible to ThT (τ − ). The generation of τ − fibril polymorphs is stochastic and can skew the apparent fibrillization kinetics revealed by ThT. Their emergence has thus been ignored so far or mistaken for fibrillization inhibitions/failures. They present a yet undescribed atomic organization and show an exacerbated propensity toward self-replication in cortical neurons, and in living mice, their injection into the substantia nigra pars compacta triggers a synucleinopathy that spreads toward the dorsal striatum, the nucleus accumbens, and the insular cortex. %G en %J Science Advances %A De Giorgi, Francesca %A Laferrière, Florent %A Zinghirino, Federica %A Faggiani, Emilie %A Lends, Alons %A Bertoni, Mathilde %A Yu, Xuan %A Grélard, Axelle %A Morvan, Estelle %A Habenstein, Birgit %A Dutheil, Nathalie %A Doudnikoff, Evelyne %A Daniel, Jonathan %A Claverol, Stéphane %A Qin, Chuan %A Loquet, Antoine %A Bezard, Erwan %A Ichas, François %D 10/2020 %K highlight peer-reviewed