Neurofibrillary tangle‐like tau pathology induced by synthetic tau fibrils in primary neurons over‐expressing mutant tau

Increasing evidence demonstrates the transmissibility of fibrillar species of tau protein, but this has never been directly tested in neurons, the cell type most affected by formation of tau inclusions in neurodegenerative tauopathies. Here we show that synthetic tau fibrils made from recombinant protein not only time-dependently recruit normal tau into neurofibrillary tangle-like insoluble aggregates in primary hippocampal neurons over-expressing human tau, but also induce neuritic tau pathology in non-transgenic neurons. This study provides highly compelling support for the protein-only hypothesis of pathological tau transmission in primary neurons and describes a useful neuronal model for studying the pathogenesis of tauopathies.