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 K. Majbour, Shiji Varghese, Fatimah Alzahmi, Katerina E. Paleologou, Dena A.M. Amer, Abdulmonem Al-Hayani, Omar M.A. El-Agnaf

Research output: Contribution to journalArticlepeer-review

52 Citations (Scopus)

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.

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

Keywords

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

ASJC Scopus subject areas

  • Ageing
  • Cognitive Neuroscience

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