APP and Alzheimer disease: Due to triplication of chromosome 21 resulting in overexpression of amyloid precursor protein and the build-up of amyloid-β in the brain, individuals with Down syndrome (DS) are predisposed to the development of AD.14, 16 Fortea et al17 described the similarity between the natural history of AD in people with DS compared with those with sporadic or autosomal dominant AD, characterised by a long preclinical phase; and they highlight the unique opportunity for research of AD in DS to gain better insight into early changes associated with future AD.