MAPT and neurodegenerative disease: While this has until now been a formidable obstruction to finding a broad-based approach to the characterization of mechanisms underlying tau toxicity and lesion spreading, it offers important hints for the direction of future studies on the topic – i.e., to focus on synaptic functions and developmental axon identity and guidance mechanisms to identify tauopathy-specific mechanisms, and to focus on aggregation-mediated mechanisms for identifying common themes of neurodegenerative disease pathogenesis.