%A Aasly,Jan O. %A Johansen,Krisztina K. %A Brønstad,Gunnar %A Warø,Bjørg J. %A Majbour,Nour K. %A Varghese,Shiji %A Alzahmi,Fatimah %A Paleologou,Katerina E. %A Amer,Dena A. M. %A Al-Hayani,Abdulmonem %A El-Agnaf,Omar M. A. %D 2014 %J Frontiers in Aging Neuroscience %C %F %G English %K Parkinson’s disease,LRRK2 Mutation Carriers,CSF,biomarkers,alpha-synuclien %Q %R 10.3389/fnagi.2014.00248 %W %L %M %P %7 %8 2014-September-25 %9 Original Research %+ Jan O. Aasly,Department of Neurology, St. Olav’s Hospital, University Hospital of Trondheim,Trondheim, Norway,Jan.Aasly@ntnu.no %+ Jan O. Aasly,Department of Neuroscience, Norwegian University of Science and Technology (NTNU),Trondheim, Norway,Jan.Aasly@ntnu.no %+ Dr Omar M. A. El-Agnaf,Department of Biochemistry, College of Medicine and Health Sciences, United Arab Emirates University,Al Ain, United Arab Emirates,o.elagnaf@uaeu.ac.ae %+ Dr Omar M. A. El-Agnaf,Faculty of Medicine, King Abdulaziz University,Jeddah, Saudi Arabia,o.elagnaf@uaeu.ac.ae %# %! CSF α-Synuclein Oligomers in Lrrk2 Cases %* %< %T Elevated levels of cerebrospinal fluid α-synuclein oligomers in healthy asymptomatic LRRK2 mutation carriers %U https://www.frontiersin.org/articles/10.3389/fnagi.2014.00248 %V 6 %0 JOURNAL ARTICLE %@ 1663-4365 %X 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.