Medin drives Aβ40 to adopt Aβ42-like fibril polymorphs in vitro.

ABSTRACT: Medin, a vascular amyloid derived from MFG-E8, is the most prevalent form of localized human amyloid and co-localizes with Aβ in Alzheimer's disease and, in particular, cerebral amyloid angiopathy (CAA). While it was shown that medin can promote Aβ aggregation, it remains unclear whether this amyloid-amyloid interaction affects the structure of the resulting fibrils. Here, we investigate how medin modulates Aβ40 fibril assembly in vitro using cryo-electron microscopy, aggregation kinetics, and immunogold electron microscopy. We show that medin accelerates Aβ40 aggregation, co-assembles into hybrid fibrils, and modulates fibril morphology. Cryo-EM analysis reveals two fibril populations: one corresponding to a previously described in vitro Aβ40 morphology, and a second, previously unobserve

SUBMITTER: Pradhan B 

PROVIDER: S-EPMC12338643 | biostudies-literature | 2025 Jul

REPOSITORIES: biostudies-literature