Single Point Mutation from E22-to-K in Aβ Initiates Early-Onset Alzheimer's Disease by Binding with Catalase.

ABSTRACT: Amyloid-beta (Aβ) is a critical etiological factor for late-onset familial Alzheimer's disease (AD). However, an early-onset AD has been found to be related with an Aβ mutation in glutamic acid 22-to-lysine (Italian type E22K). Why only one single point mutation at E22 residue induces AD remains unclear. Here, we report that a Chinese familial AD pedigree with E22K mutation was associated with higher levels of serum hydrogen peroxide (H₂O₂) and lower activity of catalase (a H₂O₂ degrading enzyme) than controls. Further, we found that E22K binding with catalase caused more severe H₂O₂ accumulation in the brains of E22K-injected rats than Aβ-injected rats. Unexpectedly, H₂O₂ bound wit

SUBMITTER: Jiang W 

PROVIDER: S-EPMC7775154 | biostudies-literature | 2020

REPOSITORIES: biostudies-literature