MAPT and early-onset autosomal dominant Alzheimer disease: Accumulation of 3R and 4R tau isoforms results in distinct clinical manifestations: tangles comprised of paired helical filaments in Alzheimer’s disease brain contain a mixture of 3R and 4R tau, whereas 4R isoforms predominate the inclusions in progressive supranuclear palsy and corticobasal degeneration brain (VandeVrede et al., 2020).