MAPT and tauopathy: Different ratios of three and four repeat (3R and 4R) tau isoforms are characteristic of tau aggregates found in specific tauopathies (26, 52) and the presence of intronic mutations interfering with the splicing of exon 10 in patients with FTDP-17 (30, 53) confirms that the resulting change in the ratio of 3R:4R tau is sufficient to drive tau filamentation and neurodegeneration (54).