APP and early-onset autosomal dominant Alzheimer disease: Precocious ageing and Alzheimer’s disease (AD) are strikingly common in DS, with almost 100% of people with DS eventually developing the neuropathology of AD [30], which is likely to be linked to the overexpression of the amyloid precursor protein gene (APP) resulting in a lifelong excess of beta-amyloid (Aβ).