Time Course of Prion Seeding Activity in Cerebrospinal Fluid of Scrapie-Infected

To assess prospects for early diagnosis of prion disease based on prion seeding activity in cerebrospinal fluid (CSF), we measured the activity over time in scrapie-infected hamsters by real-time quaking-induced conversion (RT-QuIC). After intracerebral in-oculation, activity appeared in CSF within 1 day and plateaued weeks before the onset of clinical signs. However, after intra-tongue inoculation, activity first appeared in CSF with the onset of clinical signs, well after higher-level accumulation of seeding activity in brain. Transmissible spongiform encephalopathies (TSE), or priondiseases, are fatal transmissible neurodegenerative diseases that include Creutzfeldt-Jakob disease (CJD) in humans, scrapie in sheep, bovine spongiform encephalopathy, chronic wasting disease in cervids, and transmissible mink encephalopathy. TSEs involve the conversion of the host’s normal prion protein (PrPC) to abnormal pathological forms (PrPSc) which are associated with, and largely comprise, the infectious TSE agents or prions (6). A major problem in coping with TSEs is the difficulty in diag-nosing these diseases early in their incubation period. One poten-tially useful diagnostic specimen is cerebrospinal fluid (CSF)