Alpha-Synuclein Protofibrils in Cerebrospinal Fluid: A Potential Biomarker for Parkinson's Disease

• Background: Currently, there is no established biomarker for Parkinson's disease (PD) and easily accessible biomarkers are crucial for developing disease-modifying treatments. Objective: To develop a novel method to quantify cerebrospinal fluid (CSF) levels of alpha-synuclein protofibrils (alpha-syn PF) and apply it to clinical cohorts of patients with PD and atypical parkinsonian disorders. Methods: A cohort composed of 49 patients with PD, 12 with corticobasal degeneration (CBD), 22 with progressive supranuclear palsy, and 33 controls, that visited the memory clinic but had no biomarker signs of Alzheimer's disease (AD, tau<350 pg/mL, amyloid-beta 42 (A beta(42))>530 pg/mL, and phosphorylated tau (p-tau)<60 pg/mL) was used in this study. The CSF samples were analyzed with the Single molecule array (Simoa) technology. Total alpha-synuclein (alpha-syn) levels were analyzed with a commercial ELISA-kit. Results: The assay is specific to alpha-syn PF, with no cross-reactivity to monomeric alpha-syn, or the beta- and gamma-synuclein variants. CSF la-syn PF levels were increased in PD compared with controls (62.1 and 40.4 pg/mL, respectively, p = 0.03), and CBD (62.1 and 34.2 pg/mL, respectively, p = 0.02). The accuracy of predicting PD using alpha-syn PF is significantly different from controls (area under the curve 0.68, p = 0.0097) with a sensitivity of 62.8% and specificity of 67.7%. Levels of total la-syn were significantly different between the PD and CBD groups (p = 0.04). Conclusion: The developed method specifically quantifies alpha-syn PF in human CSF with increased concentrations in PD, but with an overlap with asymptomatic elderly controls.

Subject headings

MEDICIN OCH HÄLSOVETENSKAP  -- Medicinska och farmaceutiska grundvetenskaper -- Neurovetenskaper (hsv//swe)

MEDICAL AND HEALTH SCIENCES  -- Basic Medicine -- Neurosciences (hsv//eng)

Keyword

Parkinson's disease

alpha-synuclein protofibrils

Simoa

biomarker

CSF

atypical parkinsonian disorders

neurofilament light-chain

drug-naive patients

elevated levels

clinical-features

economic-impact

protein

csf

oligomers

brain

quantification

Neurosciences & Neurology

Publication and Content Type

ref (subject category)

art (subject category)