Proteopathic Seed Amplification Assays for Neurodegenerative Disorders.

The need for etiological biomarkers for neurodegenerative diseases involving protein aggregation has prompted development of ultrasensitive cellular and cell-free assays based on the prion-like seeding capacity of such aggregates. Among them, prion RT-QuIC assays allow accurate antemortem Creutzfeldt-Jakob disease diagnosis using cerebrospinal fluid and nasal brushings. Analogous assays for synucleinopathies (e.g., Parkinson disease and dementia with Lewy bodies) provide unprecedented diagnostic sensitivity using cerebrospinal fluid. Biosensor cell and tau RT-QuIC assays can detect and discriminate tau aggregates associated with multiple tauopathies (e.g., Alzheimer disease and frontotemporal degeneration). An expanding panel of seed amplification assays should improve diagnostics and therapeutics development.