MAPT and frontotemporal dementia: Importantly, 4R tau binds microtubules with higher affinity than 3R tau, and mutations affecting exon 10 splicing can disturb the 3R:4R ratio, contributing to the development of tauopathies such as Pick's disease (3R), progressive supranuclear palsy (4R), and corticobasal degeneration (4R).