Unique pathological tau conformers from Alzheimer’s brains transmit tau pathology in nontransgenic mice

• DOI: 10.1084/jem.20160833
• Publication Date: 2016-10-17T14:33:53Z
• Authors: Jing L. Guo; Sneha Narasimhan; Lakshmi Changolkar; Zhuohao He; Anna Stieber; Bin Zhang; Ronald J. Gathagan; Michiyo Iba; Jennifer D. McBride; John Q. Trojanowski; Virginia M.Y. Lee
• Keywords: Tau Pathology

Filamentous tau aggregates are hallmark lesions in numerous neurodegenerative diseases, including Alzheimer’s disease (AD). Cell culture and animal studies showed that fibrils can undergo cell-to-cell transmission seed aggregation of soluble tau, but this phenomenon was only robustly demonstrated models overexpressing tau. In study, we found intracerebral inoculation purified from AD brains (AD-tau), not synthetic fibrils, resulted the formation abundant inclusions anatomically connected brain regions nontransgenic mice. Recombinant human seeded by AD-tau revealed unique conformational features distinct which could underlie differential potency seeding physiological levels to aggregate. Therefore, our study establishes a mouse model sporadic tauopathies points important differences between generated artificially authentic ones develop brains.