Elevated levels of cerebrospinal fluid α-synuclein oligomers in healthy asymptomatic LRRK2 mutation carriers

Jan O. Aasly, Krisztina K. Johansen, Gunnar Brønstad, Bjørg J. Warø, Nour Majbour, Shiji Varghese, Fatimah Alzahmi, Katerina E. Paleologou, Dena A M Amer, Abdulmonem Al-Hayani, Omar Ali El-Agnaf

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Abstract

Mutations in the leucine-rich repeat kinase 2 gene are the most common cause of autosomal dominant Parkinson's disease. To assess the cerebrospinal fluid levels of α-synuclein oligomers in symptomatic and asymptomatic leucine-rich repeat kinase 2 mutation carriers, we used enzyme25 linked immunosorbent assays to investigate total and oligomeric forms of α-synuclein in cerebrospinal fluid samples. The cerebrospinal fluid samples were collected from 33 Norwegian individuals with leucine-rich repeat kinase 2 mutations: 13 patients were clinically diagnosed with Parkinson's disease and 20 patients were healthy, asymptomatic leucine-rich repeat kinase 2 mutation carriers. We also included 35 patients with sporadic Parkinson's disease and 42 age-matched healthy controls. Levels of cerebrospinal fluid α-synuclein oligomers were significantly elevated in healthy asymptomatic individuals carrying leucine-rich repeat kinase 2 mutations (n = 20; P < 0.0079) and in sporadic Parkinson's disease group (n = 35; P < 0.003) relative to healthy controls. Increased α- synuclein oligomers in asymptomatic leucine-rich repeat kinase 2 mutation carriers showed a sensitivity of 63.0% and a specificity of 74.0%, with an area under the curve of 0.66, and a sensitivity of 65.0% and a specificity of 83.0%, with an area under the curve of 0.74 for sporadic Parkinson's disease cases. An inverse correlation between cerebrospinal fluid levels of α-synuclein oligomers and disease severity and duration was observed. Our study suggests that quantification of α-synuclein oligomers in cerebrospinal fluid has potential value as a tool for Parkinson's disease diagnosis and presymptomatic screening of high-risk individuals

Original languageEnglish
Article number248
JournalFrontiers in Aging Neuroscience
Volume6
Issue numberSEP
DOIs
Publication statusPublished - 2014
Externally publishedYes

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Keywords

  • Alpha-synuclien
  • Biomarkers
  • CSF
  • LRRK2 mutation carriers
  • Parkinson's disease

ASJC Scopus subject areas

  • Ageing
  • Cognitive Neuroscience

Cite this

Aasly, J. O., Johansen, K. K., Brønstad, G., Warø, B. J., Majbour, N., Varghese, S., Alzahmi, F., Paleologou, K. E., Amer, D. A. M., Al-Hayani, A., & Ali El-Agnaf, O. (2014). Elevated levels of cerebrospinal fluid α-synuclein oligomers in healthy asymptomatic LRRK2 mutation carriers. Frontiers in Aging Neuroscience, 6(SEP), [248]. https://doi.org/10.3389/fnagi.2014.00248