WHAT IT IS The assay exploits the seeded conversion of normal prion protein to the abnormal form and therefore detects disease associated prion protein in the CSF. HOW IT WORKS The assay amplifies small samples of misfolded protein collected from CSF in living patients and autopsied tissue from pathologically-confirmed cases. RT-QuIC usually starts with a small body fluid sample, usually CSF, collected from patients. Nasal brushings, urine, skin and eye components have been used for the assay. In 4-repeat tau RT-QuIC assays, a small drop of diagnostic specimen that contains the tau aggregate or “seed” is mixed with a vast excess of monomers of a recombinant 4-repeat tau fragment (that is, the substrate). The aggregates incorporate the substrate and begin growing into recombinant fibrils. A fluorescent dye is used to detect the fibrils as they accumulate. HOW IT IS APPLIED The assay has been used to detect abnormal aggregates of prion protein and tau fragments in CJD, tauopathies, Lewy body disease, and other neurodegenerative disorders.