AD is a neurodegenerative disorder with progressive cognitive decline and memory loss that correlates with dysregulation of early synaptic function and decreased spine density in the AD brain.67 The presence of active caspases before evidence of neurofibrillary tangles in tau overexpression mouse models68, 69 and increased active caspase-3 corresponding with memory decline in an AD mouse Tg2576 before detection of plaques70 suggests non-death-related roles of caspases in AD pathogenesis. Here, MAPT is linked to Alzheimer disease.