Cryo-EM structures reveal variant Tau amyloid fibrils between the rTg4510 mouse model and sporadic human tauopathies
Wanbing Zhao, Kaien Liu, Yun Fan, Qinyue Zhao, Youqi Tao, Mengwei Zhang, Linhua Gan, Wenbo Yu, Bo Sun, Dan Li, Cong Liu, Jian Wang
Abstract
Tau amyloid accumulation is a prevalent pathological feature observed in various neurodegenerative diseases such as Alzheimer’s disease (AD), corticobasal degeneration (CBD), globular glial tauopathy (GGT), familial frontotemporal lobar degeneration (FTLD), chronic traumatic encephalopathy (CTE), Pick’s disease (PiD), argyrophilic grain disease (AGD), and progressive supranuclear palsy (PSP), collectively termed tauopathies 1 , 2 . In these diseases, Tau amyloid fibrils accumulate intracellularly, leading to an array of pathological outcomes, from prion-like propagation and protein homeostasis disruption to enhanced neuroinflammatory response 3 . Importantly, recent cryo-electron microscopy (cryo-EM) studies have revealed that Tau exhibits unique amyloid fibril structures in the brains of patients across different tauopathies, correlating with specific disease variants. This underscores the critical influence of individual Tau fibril structures in steering disease progression, dictating the clinical-pathologic presentation, and providing atomic and molecular fingerprints in classifying tauopathy subtypes 4 , 5 .