ABSTRACT
A principal constituent of Alzheimer’s disease amyloid plaques is the human amyloid-ß-peptide (Aß), a 3943 amino acid peptide of known primary sequence. Currently, it is widely believed that Aß deposits contribute directly to the disease’s progressive neurodegeneration. The Arctic mutant was shown to form aggregates and fibrils at much lower concentrations. Initially, the self-aggregation process is characterized as a slow transition of aggregates to a highly distinct and ordered morphology, putatively, a key kinetic intermediates, so called spherical bodies. Then, the process proceeds with rapid polymerization of the peptides into amyloid fibrils. Interestingly, the Arctic mutant amyloid fibrils exhibit a large variety of polymorphs: both coiled and non-coiled fibril structures of at list five distinct types were recognized and their dimensions were measured precisely by atomic force microscope. Peptides were synthesized on a Perkin Elmer 433A peptide synthesizer using solid-phase fast F-moc synthesis and HPLC purified as described in N. Oleg. Antzutkin et al.
