Altered processing of amyloid protein from its precursor (amyloid precursor protein, APP) is now recognised as the key to the pathogenesis of AD. This conclusion is based on several lines of evidence, particularly the genetic analysis of certain, relatively rare, types of familial AD, in which mutations of the APP gene, or of other genes (e.g. for presenilins and sortilin-related receptor 1) that control amyloid processing, have been discovered. The APP gene resides on chromosome 21, of which an extra copy is the cause of Down’s syndrome, in which early AD-like dementia occurs in association with overexpression of APP.