Structural heterogeneity of CTE Type I tau filaments with an interface-shifted polymorph

Abstract

Tau filament types can differ in inter-protofilament packing while sharing the same protofilament fold. Motivated by our recent findings in vacuolar tauopathy, we analyzed cryo-electron microscopy (cryo-EM) data from brain-derived chronic traumatic encephalopathy (CTE) tau filaments deposited in EMPIAR-10313. We resolved the canonical CTE Type I structure and a previously unreported CTE Type I-like structure with a shifted protofilament interface at 2.78 and 2.96 A, respectively. Mapping particle-state assignments back onto the original micrographs showed that the CTE Type I and CTE Type I-like packing states can occupy locally contiguous regions within the same fibrils. These findings identify an interface-shifted CTE Type I-like structure and support its local coexistence with CTE Type I within individual fibrils.