PSEN1 and Alzheimer disease: Although the aetiology of AD is complex and far from understood, the identification of several (albeit relatively rare) mutations in genes such as APP (which encodes amyloid precursor protein) and PS1 and PS2 (which encode presenilin 1 and 2, which are involved in the metabolism of APP) has led to the overarching ‘amyloid’ hypothesis, which states that overexpression of β-amyloid is involved in the pathology of AD.