APP and early-onset autosomal dominant Alzheimer disease: APP generates β-amyloid, which is the primary component of the amyloid plaques found in DS and Alzheimer disease (AD) brains.35 It has been shown that DS patients by the age of 40 have neuropathological changes that are consistent with AD,36 thus DS patients tend to develop dementia 10–20 years earlier than the general population.35 This was also evident from our analysis where non-mosaic patients have a RR of 31.39 of developing AD and the median age of onset was 53 years (Table S6).