CSF Biomarker Flags Parkinson's Pathology Much Earlier

There were 52 patients with IRBD and 40 healthy controls matched for age, sex and duration of follow-up underwent lumbar puncture between March 23, 2008, and July 16, 2017. CSF samples were stored until analyzed using RT-QuIC.

The team reported that during follow-up, 32 patients (62%) were diagnosed with Parkinson's disease or dementia with Lewy bodies a mean 3.4 years after lumbar puncture, of whom 31 (97%) were α-synuclein positive at baseline. Specifically, 16 people developed Parkinson's (15 of whom were positive for CSF α -synuclein), and 16 developed dementia with Lewy bodies (all were positive for CSF α-synuclein). CSF α-synuclein RT-¬QuIC was positive in 47 (90%) of 52 patients and in four (10%) of 40 healthy controls, resulting in a sensitivity of 90.4% (95% CI 79.4–95.8) and a specificity of 90.0% (95% CI 76.9–96.0).

The average interval for people who were alpha-synuclein positive at baseline to convert to clinically defined Parkinson's or dementia with Lewy bodies was 3.2 years. Patients with IRBD who were α-synuclein negative had lower risk for developing Parkinson's disease or dementia with Lewy bodies at 2, 4, 6, 8, and 10 years of follow-up than patients with IRBD who were α-synuclein positive. During follow-up, none of the controls developed an α-synucleinopathy.

Alison Green, PhD, a Reader in Biochemistry and a senior author of the study, said, “The detection of pathological α-synuclein preceded the development of clinical symptoms by a mean of 3.2 years, with a range of 6 months to 9 years. This is the first step towards having a reliable biomarker for early, pre-symptomatic disease which will enable therapeutic interventions, including potential neuroprotective treatments, to start in a timelier manner.”

The authors concluded that in patients with IRBD, RT-QuIC detects misfolded α-synuclein in the CSF with both sensitivity and specificity of 90%, and α-synuclein positivity was associated with increased risk of subsequent diagnosis of Parkinson's disease or dementia with Lewy bodies. Detection of α-synuclein in the CSF represents a potential prodromal marker of Parkinson's disease and dementia with Lewy bodies. The study was published on March 1, 2021 in the journal Lancet Neurology.


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