Of particular note, Casp2-mediated tau cleavage at amino acid residue aspartate 314 (D314) (tau 2N4R isoform numbering system hereafter unless specified) is responsible for synaptic function impairment and cognitive deficits in cellular and transgenic mouse models of frontotemporal dementia and parkinsonism linked to chromosome 17 [44], indicating a toxic partnership between Casp2 and tau [36]. This evidence concerns the gene MAPT and frontotemporal dementia.