Isoaspartate formation at position 23 of amyloid beta peptide enhanced fibril formation and deposited onto senile plaques and vascular amyloids in Alzheimer's disease

Open Access
Publisher Website
Google Scholar
Abstract
Senile plaques and amyloid‐bearing vessels consisting of fibrillar amyloid β peptides (Aβ) are characteristic neuropathological features of Alzheimer's disease (AD). Aβ undergo spontaneous post‐translational modifications, such as isomerization and racemization, at their aspartyl residues in AD brains. Here we present evidence that Aβ isomerized at position 23 are deposited on plaques and vascular amyloids using an anti‐isomerized Aβ antibody. In vitro experiments showed that isomerization at position 23, but not position 7, enhanced aggregation. Furthermore, Aβ with the Dutch mutation, but not the Flemish mutation, also showed greatly enhanced aggregation. These results suggest that mutations or modifications at positions Glu22 and Asp23 have a pathogenic role in the deposition of Aβ. The development and progression of sporadic AD may be accelerated by spontaneous isomerization at position 23 of Aβ.

This publication has 34 references indexed in Scilit: