Due to improved healthcare, individuals with DS have experienced a significant increase in average life span the last few decades but suffer from an increased incidence of early onset AD and associated amyloid [37], phospho-tau [38, 57, 72] and neurotransmitter cellular dysfunction [4, 11, 28, 32, 49, 54] compared to the general population [36, 79, 80]. Here, MAPT is linked to Alzheimer disease.