Yann Fichou's Tau Research Published in Nature Structural & Molecular Biology

"Brain deposits of tangles made of tau proteins a direct diagnosis for chronic traumatic encephalopathy (CTE). Current state-of-the-art medical tools cannot directly diagnose CTE without postmortem analysis of brain tissue, let alone delay or modify disease progression.

Different tauopathies, which are known to involve different tau variants, have long been hypothesized to be associated with different filament structures. Most recently, the structure of tau filaments derived from postmortem brain of three patients who died from CTE was published by Falcon, Goedert, Scheres and co-workers, who used cryo-EM to resolve two filament structures to a resolution of 2.3 Å. The two different filaments, called ‘type I’ and ‘type II’, are composed of the same protofilaments, but differ in the interface between these protofilaments. This study demonstrates, for the first time, that the same tau variant and isoform mixture can generate distinct tau filaments in the context of AD versus CTE.

A recent study by Zhang et al. and our own study have demonstrated that tau aggregation in vitro, induced by the most widely used cofactor, heparin, generates tau filament models that are structurally heterogeneous and different from postmortem tissues from people with AD, PiD or CTE. These findings illustrate the considerable structural versatility of tau amyloid filaments and hence both challenge the biological relevance of tau filament models formed by heparin and highlight the need to achieve specific structural convergence."