α-Synuclein RT-QuIC assay in cerebrospinal fluid of patients with dementia with Lewy bodies

Abstract

We applied RT-QuIC assay to detect α-synuclein aggregates in cerebrospinal fluid (CSF) of patients with suspected Creutzfeldt-Jakob disease who had a neuropathological diagnosis of dementia with Lewy bodies (DLB) (n = 7), other neurodegenerative diseases with α-synuclein mixed pathology (n = 20), or without Lewy-related pathology (n = 49). The test had a sensitivity of 92.9% and specificity of 95.9% in distinguishing α-synucleinopathies from non-α-synucleinopathies. When performed in the CSF of patients with DLB (n = 36), RT-QuIC was positive in 17/20 with probable DLB, 0/6 with possible DLB, and 0/10 with Alzheimer disease. These results indicate that RT-QuIC for α-synuclein is an accurate test for DLB diagnosis.

Figure 1

Results of α‐synuclein Real‐Time Quaking‐Induced Conversion (RT‐QuIC) assay of CSF samples from neuropathologically confirmed cases (A), α‐syn co‐pathology (B) and clinical cases (C). Traces represent the average percentage of Thioflavin T (ThT) fluorescence from four replicate reactions (normalized as described in the Methods section) with the means (thick lines) of those average and SDs (thin lines) shown as a function of RT‐QuIC reaction time; (Panel A) Curves representative of α‐syn RT‐QuIC from seven patients with pure DLB (blue trace) and 20 patients with α‐syn co‐pathology (LBD/AD; LBD/PART, and CJD/LBD) (burgundy trace), and from 49 control with other neurodegenerative and neurological diseases (green trace); (Panel B) Curves representative of RT‐QuIC results in different groups with α‐syn co‐pathology; (Panel C) Curve representative of CSF samples positive to α‐syn RT‐QuIC from 17 patients with clinical diagnosis of probable DLB (blue trace) and 19 negative samples (green trace), which include three patients with probable DLB, six with possible DLB and 10 with AD.