Amyloid fibrils’ ‘mystery density’ begins to take shape

Amyloid fibrils appear in many neurodegenerative diseases, and scientists are eager to understand how they form and spread. But amyloids—clumped aggregations of misfolded proteins—can be difficult to study. Certain proteins can adopt multiple distinct amyloid shapes, and recent research has shown that the fibrils that researchers grow in laboratories to study are shaped differently than fibrils isolated from the brains of people with neurodegenerative diseases. In α-synuclein fibrils from people with multiple system atrophy, for example, researchers have identified a structure not observed in lab-grown fibrils. In the fibrils from brains, electron density maps suggest a molecule distinct from α-synuclein is present but it can’t be identified ( Nature 2020, DOI: 10.1038/s41586-020-2317-6 ). In a study published today, researchers in Ursula Jakob’s lab at the University of Michigan argue that the mystery density is most likely polyphosphate ( PLOS Biol. 2024, DOI: 10.1371/journal.pbio.3002650 ). Despite polyphosphate’s simple linear structure researchers