Lessons from the Study of Covalent Dimers of the Alzheimer’s Disease-Associate Amyloid β-Protein

Alzheimer’s disease (AD) is a brain disorder that first manifests in the form of intermittent memory problems and then progresses to dementia and ultimately death. Although the precise cause of AD remains obscure evidence from multiple sources indicate that the amyloid β-protein (Aβ) plays a key role [1]. Aβ comprises a family of proteins with a common core of ~30 amino acids. These peptides are amphipatic in nature and are prone to self-associate and certain aggregates of Aβ are toxic to nerve cells. Aβ of various sequences, but most particularly those that extend C-terminal to alanine 42, are found in the tell-tale amyloid plaques which litter the brains of individuals who die with AD. Several mutations within the Aβ sequence cause early onset AD and are believed to increase the formation of toxic Aβ assemblies. However, such mutations are very rare and most cases of AD occur in individuals with the normal Aβ sequence