A possible mechanism for the enhanced toxicity of beta-amyloid protofibrils in Alzheimer's disease.

ABSTRACT: The amyloid-beta peptide (Aβ) is a driver of Alzheimer's disease (AD). Aβ monomers can aggregate and form larger soluble (oligomers/protofibrils) and insoluble (fibrils) forms. There is evidence that Aβ protofibrils are the most toxic form, but the reasons are not known. Consistent with a critical role for this form of Aβ in AD, a recently FDA-approved therapeutic antibody targeted against protofibrils, lecanemab, slows the progression of AD in patients. The plasma contact system, which can promote coagulation and inflammation, has been implicated in AD pathogenesis. This system is activated by Aβ which could lead to vascular and inflammatory pathologies associated with AD. We show here that the contact system is preferentially activated by protofibrils of Aβ. Aβ protofibrils bind to coagu

SUBMITTER: Chen ZL 

PROVIDER: S-EPMC10483626 | biostudies-literature | 2023 Sep

REPOSITORIES: biostudies-literature