MAPT and Alzheimer disease: People with DS develop Alzheimer’s disease (AD)-like (AD-DS) pathology of Aβ plaques and accumulation of tangles of hyperphosphorylated Tau leading to neurodegeneration in people as young as 20 years old, causing progressive motor, cognitive and health decline in early middle age33,34 and, finally, shortening of life by ~ 30 years35.