Optogenetic model of tau aggregation for tauopathies

Alzheimer’s disease (AD) and >20 other dementias, termed tauopathies, are pathologically defined by insoluble aggregates of the microtubule‐associated protein tau (MAPT). A predictive relationship between the onset and progression of clinical AD symptoms correlates with post‐translational modifications of tau in cerebrospinal fluid and tau aggregation in the brains of AD patients. However, the biological basis for the transition of tau from a microtubule‐associated protein to an insoluble aggregate and the precise relationship between tau aggregation and neuronal dysfunction remains unknown. Recent studies have reported the development of photo‐inducible systems to control protein aggregation using photo‐oligomerizable proteins that self‐associate upon exposure to blue light. We hypothesized that the development of a photo‐inducible system, which permits temporal control of tau aggregation, would provide a novel tool to study the cause and consequence of tau aggregation.