Transient dynamics of Aβ contribute to toxicity in Alzheimer’s disease

The aggregation and deposition of the amyloid-beta peptide (Abeta) in the brain has been linked with neuronal death, which progresses in the diagnostic and pathological signs of Alzheimer's disease (AD). The transition of an unstructured monomeric peptide into self-assembled and more structured aggregates is the crucial conversion from what appears to be a harmless polypeptide into a malignant form that causes synaptotoxicity and neuronal cell death. Despite efforts to identify the toxic form of Abeta, the development of effective treatments for AD is still limited by the highly transient and dynamic nature of interconverting forms of Abeta. The variability within the in vivo "pool" of different Abeta peptides is another complicating factor. Here we review the dynamical interplay between various components that influence the heterogeneous Abeta system, from intramolecular Abeta flexibility to intermolecular dynamics between various Abeta alloforms and external factors. The complex dynamics of Abeta contributes to the causative role of Abeta in the pathogenesis of AD.

Publication year:2014

Keywords:Alzheimer's disease, amyloid-beta peptide, Abeta dynamics, Intrinsically disordered peptide, Aggregation