Alpha-Synuclein RT-QuIC: An Ultrasensitive Assay for the Detection of Alpha-Synuclein Seeding Activity Associated with Synucleinopathies

Synucleinopathies are a category of neurodegenerative diseases defined by the abnormal aggregation and accumulation of misfolded alpha-synuclein protein molecules within the brain. These aggregates are of particular concern to humans as they are a primary cause of Parkinson’s disease, dementia with Lewy bodies, and other neurological disorders. This technology enables rapid, economical and ultrasensitive detection of disease-associated forms of alpha-synuclein as biomarkers or indicators of synucleinopathy in a biological sample. Specifically, alpha-synuclein aggregates (contained in a biological sample) seed the polymerization of vast stoichiometric excesses of recombinant, normally folded alpha-synuclein into amyloid fibrils that are then detectable by an amyloid-sensitive fluorescent dye. This reaction can thereby amplify the seeds in a biospecimen by many orders of magnitude. For example, in its current embodiment, this assay has been used to detect alpha-synuclein seeds in cerebral spinal fluid from living patients with Parkinson’s disease and Lewy-body dementia, giving high diagnostic sensitivity and specificity with unprecedented speed.

This technology is available for licensing for commercial development in accordance with 35 U.S.C. § 209 and 37 CFR Part 404.