text: Amyloid-beta precursor protein is an ancient and highly conserved protein.  In humans, the gene APP is located on chromosome 21 and contains 18 exons spanning 290 kilobases. Several alternative splicing isoforms of APP have been observed in humans, ranging in length from 639 to 770 amino acids, with certain isoforms preferentially expressed in neurons; changes in the neuronal ratio of these isoforms have been associated with Alzheimers disease. Homologous proteins have been identified in other organisms such as Drosophila (fruit flies), C. elegans (roundworms), and all mammals. The amyloid beta region of the protein, located in the membrane-spanning domain, is not well conserved across species and has no obvious connection with APPs native-state biological functions.
  Mutations in critical regions of amyloid precursor protein, including the region that generates amyloid beta (Aβ), cause familial susceptibility to Alzheimers disease. For example, several mutations outside the Aβ region associated with familial Alzheimers have been found to dramatically increase production of Aβ.
  A mutation (A673T) in the APP gene protects against Alzheimer's disease.  This substitution is adjacent to the beta secretase cleavage site and results in a 40% reduction in the formation of amyloid beta in vitro.