Figure 1: Tau splice isoforms, mutations, and splicing. (a) Alternative splicing of exon 10 results in tau isoforms with either 3 or 4 microtubule-binding repeat domains (3R or 4R tau). Alternative splicing of exons 2 and 3 is not shown. Site of FTLD-associated exonic mutations is indicated. Some of these mutations are silent and/or alter exon 10 splicing (red). Some of these mutations are also specific for the 4R isoforms of tau (bracket). (b) Stem-loop structure at the junction between exon 10 and intron 10. Site of FTLD-associated mutations in this structure destabilizing the stem-loop, increasing access to splicing factors and exon 10 inclusion, and resulting in increased 4R over 3R tau isoforms.