APP and Alzheimer disease: Dementia is a common feature of the aging process in DS that is due to the triplication of the amyloid precursor protein on chromosome 21, leading to brain pathology indicative of Alzheimer’s disease (AD) [1], with a cumulative incidence for dementia in excess of 90% by the age of 65 [2] and a mean age at dementia diagnosis of 55 [3].