The key discovery directly involving tau protein in neurodegeneration and dementia came from the finding that highly penetrant, dominant mutations in the MAPT gene encoding tau cause an inherited form of frontotemporal dementia and parkinsonism (Hutton et al., 1998; Poorkaj et al., 1998; Spillantini et al., 1998). This evidence concerns the gene MAPT and frontotemporal dementia.