These issues are of high relevance for this and other studies because: (i) Alzheimer’s disease is characterized by balanced 3R/4R isoforms, while PSP pathology is mainly a 4R isoform tauopathy (Buée and Delacourte, 1999; Espinoza et al., 2008); and (ii) the toxicity of tau aggregates may be driven by oligomers rather than tangles. This evidence concerns the gene MAPT and early-onset autosomal dominant Alzheimer disease.