Age-dependent structural evolution of a functional amyloid contributes to memory impairment in Drosophila.

Orb2 amyloid in Drosophila melanogaster shifts with age from translation-promoting assemblies to destabilization-resistant, translation-deficient structures linked to memory impairment.

• Why it matters: It is unclear how amyloid filaments assemble and structurally evolve in living brains, and how those transitions relate to synaptic function and behavior.
• What they did: The study mapped an age-dependent Orb2 amyloid structural landscape across the adult lifespan using multiple cryogenic electron microscopy structures, then tested memory effects by manipulating brain chaperones to bias Orb2 states.
• The result: Aging shifts the Orb2 ensemble toward aged-like, translation-deficient assemblies that coincide with memory impairment; biasing Orb2 toward youthful states improves memory in old flies, while aged-like shifting in young adults is associated with premature impairment.

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