The use of mouse models to study cell-to-cell transmission of pathological tau.

Tau protein aggregates are found in a variety of neurodegenerative diseases known as tauopathies. Emerging evidence shows tau can propagate from cell-to-cell by seeding endogenous tau to aggregate. Studies in tau transgenic mice showed intracerebrally injecting misfolded tau seeds initiates and transmits tau pathology across the mouse brain. However, transgenic mice that overexpress human tau with disease-associated mutations do not fully recapitulate sporadic tauopathies. Here, we present our method for developing a sporadic tauopathy model using pathological tau extracted from human Alzheimer's disease (AD) brains. We describe a novel method for sequentially extracting tau pathologies from human AD brain in high yield and purity. We then describe how to intracerebrally inject this extract into a nontransgenic mouse brain and analyze the transmission of tau pathology. This novel sporadic tauopathy model can be used to study the transmission of tau aggregates and test new tau-directed therapies.