Making tau amyloid models in vitro: a crucial and underestimated challenge

The protein Tau accumulates in the brain as insoluble deposits in a number of neurodegenerative diseases called tauopathies. In vitro work studying the properties of reconstituted tau assemblies has played a major role in understanding the fundamental mechanisms underlying tauopathies. Yet, in our view, the extent to which tau in vitro models represent the assemblies found in the brain is not sufficiently addressed. Here, we provide an overview of the procedures used to form tau amyloids in vitro and we discuss their similarities and differences with brain deposits. We emphasize that, to date, further work is needed to establish how to form accurate models of tau deposits with recombinant protein, let alone how to represent disease-specific properties that discriminate tauopathies.