MAPT and frontotemporal dementia: In disease conditions, tau becomes hyperphosphorylated, dissociates from microtubules and deposits in aggregates.83 FTD causative mutations occur throughout the MAPT gene but are enriched in the C-terminal region in and around the microtubule binding domains; indeed some are specific to the 4R isoforms as they are encoded in exon 10.84 Mutations frequently alter tau splicing85 and decrease the ability of tau to interact with microtubules, thereby increasing cytosolic tau aggregation.86