Proteopathic tau seeding predicts tauopathy in vivo

Prion-like propagation of proteopathic seeds may underlie the progression of neurodegenerative diseases, including the tauopathies and synucleinopathies. We aimed to construct a versatile and simple cell assay to sensitively and specifically detect proteopathic seeding activity. Using a combination of FRET flow cytometry and a tau monoclonal FRET biosensor cell line, we report seed detection in the femtomolar range. This assay is easily applied to human brain homogenates and selectively responds to Alzheimer's disease but not Huntington's disease brains. By comparing seeding activity in a mouse model of human tauopathy, we demonstrate detection of proteopathic seeding far in advance of standard histopathological markers. Proteopathic seeding is thus an early marker of tauopathy, consistent with a causal role for tau seeds in neurodegeneration.