CSF PrP-amyloid seeding predicts clinical onset in inherited prion disease

Silent proteopathic seed propagation is hypothesised to precede neurodegenerative disease, but direct evidence that it signals near-term clinical conversion in humans is lacking. In prion disease, a prototypic disorder of proteopathic seeding, cerebrospinal fluid (CSF) real-time quaking-induced conversion (RT-QuIC) offers a direct measure of prion protein amyloid seeding activity. We analysed longitudinal CSF RT-QuIC data from 94 PRNP E200K mutation carriers across international natural history cohorts to determine whether seeding status predicts clinical conversion. Eleven carriers developed

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