Alpha-synuclein RT-QuIC in the CSF of patients with alpha-synucleinopathies

Graham Fairfoul, Lynne I McGuire, Suvankar Pal, James W Ironside, Juliane Neumann, Sharon Christie, Catherine Joachim, Margaret Esiri, Samuel G Evetts, Michal Rolinski, Fahd Baig, Claudio Ruffmann, Richard Wade-Martins, Michele T M Hu, Laura Parkkinen, Alison J E Green, Graham Fairfoul, Lynne I McGuire, Suvankar Pal, James W Ironside, Juliane Neumann, Sharon Christie, Catherine Joachim, Margaret Esiri, Samuel G Evetts, Michal Rolinski, Fahd Baig, Claudio Ruffmann, Richard Wade-Martins, Michele T M Hu, Laura Parkkinen, Alison J E Green

Abstract

We have developed a novel real-time quaking-induced conversion RT-QuIC-based assay to detect alpha-synuclein aggregation in brain and cerebrospinal fluid from dementia with Lewy bodies and Parkinson's disease patients. This assay can detect alpha-synuclein aggregation in Dementia with Lewy bodies and Parkinson's disease cerebrospinal fluid with sensitivities of 92% and 95%, respectively, and with an overall specificity of 100% when compared to Alzheimer and control cerebrospinal fluid. Patients with neuropathologically confirmed tauopathies (progressive supranuclear palsy; corticobasal degeneration) gave negative results. These results suggest that RT-QuiC analysis of cerebrospinal fluid is potentially useful for the early clinical assessment of patients with alpha-synucleinopathies.

Figures

Figure 1
Figure 1
RT‐QuIC responses observed with reactions seeded with brain homogenates A, B, and CSF samples C–H. (A) Frontal cortex: DLB (light blue); AD, sCJD, SD, and unseeded reactions (gray); (B) Frontal cortex: DLB (light blue); mixed AD/DLB (dark green), mixed sCJD/DLB (purple), mixed AD/PD (light green), AD (yellow), sCJD (pink), SD (dark blue), unseeded reaction (gray); (C) CSF from two DLB patients (red, light blue) and one sCJD patient (pink); (D) CSF from 10 control patients (red); (E) CSF from 12 AD patients (yellow); (F) CSF from six DLB patients (dark blue); (G) CSF from seven mixed DLB/AD patients (dark green), frontal cortex DLB (e–h) (light blue); (H) CSF from four PD patients (one negative for RT‐QuIC) (light green) and four controls (red). A, D–H: reactions performed in duplicate and mean of duplicates illustrated; B, C: reactions performed in duplicate and both duplicates illustrated. CJD, Creutzfeldt–Jakob disease; CSF, cerebrospinal fluid; DLB, Lewy bodies; SD, sudden death.

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