Development of a robust, physiologically relevant neuronal tau aggregation assay for tau-related drug discovery.

ABSTRACT: Therapeutic interventions to block extracellular tau seeding to prevent endogenous tau aggregation and progression of Alzheimer's disease pathology are currently being investigated in clinical trials. However, the translation of promising preclinical findings to benefit clinical outcomes remains problematic due to the lack of pathophysiological models that recapitulate key features of sporadic Alzheimer's disease-related tauopathies. We developed a primary neuronal tau (hTau) seeding and propagation model. Neurons expressing wild-type human tau protein at a physiological level, seeded with a sub-nanomolar tau derived from Alzheimer's disease brain tissues, rapidly and robustly form tau aggregates and develop impaired mitochondrial function. Resulting aggregates are quantitatively measured

SUBMITTER: Wu JW 

PROVIDER: S-EPMC12670552 | biostudies-literature | 2025 Oct

REPOSITORIES: biostudies-literature