In 1984, Beyreuther and Masters purified and sequenced the amyloid constituent of the plaque in Alzheimer’s disease, and three years later, their group used this sequence to clone the gene encoding the Aβ amyloid peptide located on chromosome 21. These studies demonstrated that the Aβ amyloid was derived by proteolytic cleavage of a neuronal transmembrane receptor. Subsequent studies by many groups has shown that a variety of Aβ-amyloid oligomers lie at the centre of AD pathogenesis, and these are now the validated primary targets for both diagnostic and therapeutic strategies. Masters and Beyreuther therefore defined the principal molecular and genetic pathways leading to the current Aβ amyloid theory of causation of Alzheimer’s disease.