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Schlagwörter:
Body fluid biomarkers; Neurodegeneration; Prion; Quantitative real-time quaking-induced conversion; Urine
Zusammenfassung:
Prion diseases are fatal neurodegenerative diseases characterized by accumulation of the pathogenic prion protein PrP in the brain. We established quantitative real-time quaking-induced conversion for the measurement of minute amounts of PrP in body fluids such as urine. Using this approach, we monitored the efficacy of antiprion therapy by quantifying the seeding activity of PrP from the brain and urine of mice after prion infection. We found that the aggregation inhibitor anle138b decreased the levels of PrP in the brain and urine. Importantly, variations of PrP levels in the urine closely corresponded to those in the brain. Our findings indicate that quantification of urinary PrP enables measurement of prion disease progression in body fluids and can substitute for immunodetection in brain tissue. We expect PrP quantification biologic fluids (such as urine and cerebrospinal fluid) with quantitative real-time quaking-induced conversion to emerge as a valuable noninvasive diagnostic tool for monitoring disease progression and the efficacy of therapeutic approaches in animal studies and human clinical trials of prion diseases. Moreover, highly sensitive methods for quantifying pathologic aggregate seeds might provide novel molecular biomarkers for other neurodegenerative diseases that may involve prion-like mechanisms (protein aggregation and spreading), such as Alzheimer disease and Parkinson disease.
