Atomic structures of medin and Aβ fibrils reveal polymorphic remodeling in mixed amyloid systems

Cryo-EM structures of fibrils from defined in vitro mixtures of Aβ40 and medin resolve three populations, including a novel Aβ40 polymorph and the first full-length medin fibril structure.

• Why it matters: Mixed amyloid environments in ageing humans can contain coexisting aggregation-prone species, but how Aβ and medin interaction reshapes fibril polymorphism remains unclear.
• What they did: The study used cryo-electron microscopy to determine structures of fibrils formed from defined Aβ40–medin mixtures, alongside biochemical and immunogold analyses to assess Aβ–medin association.
• The result: Aβ and medin are associated within mixed assemblies, yet the novel Aβ polymorph’s cryo-EM map does not unambiguously resolve medin in the ordered Aβ core, implying mixture-driven remodeling via heterotypic interactions or partial, heterogeneous medin incorporation.