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.

More recent studies from Masters and colleagues have also demonstrated the time-course over which the Aβ accumulates in the evolution of Alzheimer’s disease, using molecular PET- Aβ imaging, allowing the preclinical and prodromal stages to be identified during life. They have also identified some of the genetic determinants which affect the rates of cognitive decline. These insights into the natural history of Alzheimer’s disease will have a major impact on clinical trial design and provide prognostic information for subjects at risk.