Alzheimer's disease

Aβ1-42 is the main component of amyloid plaques found frequently in the central nervous system of Alzheimer's disease patients. After it is cleavage from amyloid precursor protein, the conformation of this peptide goes through major changes during its aggregation, from monomers through oligomers to fibrils. The experimental investigation of the aggregation process of Aβ1-42 is a difficult task, mainly because of the ill-defined initial aggregation state of this oligopeptide. A possible solution for this problem is the application of the hardly aggregating Ab isopeptide, containing a depsipeptide bond formed between the Gly25 and Ser26 residues at acidic pH, which transforms to the normal Aβ1-42 structure at physiological conditions. Thus, using this isopeptide, the aggregation process can be initiated by pH switching.
According to the recent experimental studies, the presence of divalent cations (i.e. Ca2+/Mg2+) influences the aggregation propensities of Aβ1-42 and its isopeptide form differently. This difference may originate from the different starting conformation of the two investigated peptides. This conformation may be strongly influenced by the HFIP treatment of lyophilized stocks of Aβ- peptide, which is used for the removal of any preexisting structures from aggregated amyloid preparations. In this study, we investigated the structural features of Aβ1-42 and Aβ isopeptide monomers, which may help to understand the
origins of dissimilarity of the aggregation properties of the two Aβ forms.

 

Abeta

Structure of Aβ1-42 monomer