title: Elevated levels of cerebrospinal fluid α-synuclein oligomers in healthy asymptomatic LRRK2 mutation carriers.
abstract: Mutations in the leucine-rich repeat kinase 2 gene are the most common cause of autosomal dominant Parkinson's disease (PD). To assess the cerebrospinal fluid (CSF) levels of α-synuclein oligomers in symptomatic and asymptomatic leucine-rich repeat kinase 2 mutation carriers, we used enzyme-linked immunosorbent assays (ELISA) to investigate total and oligomeric forms of α-synuclein in CSF samples. The CSF samples were collected from 33 Norwegian individuals with leucine-rich repeat kinase 2 mutations: 13 patients were clinically diagnosed with PD and 20 patients were healthy, asymptomatic leucine-rich repeat kinase 2 mutation carriers. We also included 35 patients with sporadic PD (sPD) and 42 age-matched healthy controls. Levels of CSF α-synuclein oligomers were significantly elevated in healthy asymptomatic individuals carrying leucine-rich repeat kinase 2 mutations (n = 20; P < 0.0079) and in sPD 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 sPD cases. An inverse correlation between CSF levels of α- synuclein oligomers and disease severity and duration was observed. Our study suggests that quantification of α-synuclein oligomers in CSF has potential value as a tool for PD diagnosis and presymptomatic screening of high-risk individuals.
authors.affiliation: Department of Neuroscience, Norwegian University of Science and Technology (NTNU) Trondheim, Norway ; Department of Neurology, St. Olav's Hospital, University Hospital of Trondheim Trondheim, Norway.
authors.forename: Jan O
authors.initials: JO
authors.lastname: Aasly
authors.affiliation: Department of Neuroscience, Norwegian University of Science and Technology (NTNU) Trondheim, Norway.
authors.forename: Krisztina K
authors.initials: KK
authors.lastname: Johansen
authors.affiliation: Department of Neurology, St. Olav's Hospital, University Hospital of Trondheim Trondheim, Norway.
authors.forename: Gunnar
authors.initials: G
authors.lastname: Brønstad
authors.affiliation: Department of Neuroscience, Norwegian University of Science and Technology (NTNU) Trondheim, Norway ; Department of Neurology, St. Olav's Hospital, University Hospital of Trondheim Trondheim, Norway.
authors.forename: Bjørg J
authors.initials: BJ
authors.lastname: Warø
authors.affiliation: Department of Biochemistry, College of Medicine and Health Sciences, United Arab Emirates University Al Ain, United Arab Emirates.
authors.forename: Nour K
authors.initials: NK
authors.lastname: Majbour
authors.affiliation: Department of Biochemistry, College of Medicine and Health Sciences, United Arab Emirates University Al Ain, United Arab Emirates.
authors.forename: Shiji
authors.initials: S
authors.lastname: Varghese
authors.affiliation: Department of Biochemistry, College of Medicine and Health Sciences, United Arab Emirates University Al Ain, United Arab Emirates.
authors.forename: Fatimah
authors.initials: F
authors.lastname: Alzahmi
authors.affiliation: Department of Molecular Biology and Genetics, Democritus University of Thrace Alexandroupolis, Greece.
authors.forename: Katerina E
authors.initials: KE
authors.lastname: Paleologou
authors.affiliation: Department of Biochemistry, College of Medicine and Health Sciences, United Arab Emirates University Al Ain, United Arab Emirates.
authors.forename: Dena A M
authors.initials: DA
authors.lastname: Amer
authors.affiliation: Department of Anatomy, Faculty of Medicine, King Abdulaziz University Jeddah, Saudi Arabia.
authors.forename: Abdulmonem
authors.initials: A
authors.lastname: Al-Hayani
authors.affiliation: Department of Biochemistry, College of Medicine and Health Sciences, United Arab Emirates University Al Ain, United Arab Emirates ; Faculty of Medicine, King Abdulaziz University Jeddah, Saudi Arabia.
authors.forename: Omar M A
authors.initials: OM
authors.lastname: El-Agnaf
keywords: CSF; LRRK2 mutation carriers; Parkinson’s disease; alpha-synuclien; biomarkers