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

Research output: Contribution to journalArticle

30 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. 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

Fingerprint

Synucleins
Leucine
Cerebrospinal Fluid
Phosphotransferases
Parkinson Disease
Mutation
Area Under Curve
Immunosorbents

Keywords

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

ASJC Scopus subject areas

  • Ageing
  • Cognitive Neuroscience

Cite this

Elevated levels of cerebrospinal fluid α-synuclein oligomers in healthy asymptomatic LRRK2 mutation carriers. / Aasly, Jan O.; Johansen, Krisztina K.; Brønstad, Gunnar; Warø, Bjørg J.; Majbour, Nour; Varghese, Shiji; Alzahmi, Fatimah; Paleologou, Katerina E.; Amer, Dena A M; Al-Hayani, Abdulmonem; Ali El-Agnaf, Omar.

In: Frontiers in Aging Neuroscience, Vol. 6, No. SEP, 248, 2014.

Research output: Contribution to journalArticle

Aasly, JO, Johansen, KK, Brønstad, G, Warø, BJ, Majbour, N, Varghese, S, Alzahmi, F, Paleologou, KE, Amer, DAM, 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, vol. 6, no. SEP, 248. https://doi.org/10.3389/fnagi.2014.00248
Aasly, Jan O. ; Johansen, Krisztina K. ; Brønstad, Gunnar ; Warø, Bjørg J. ; Majbour, Nour ; Varghese, Shiji ; Alzahmi, Fatimah ; Paleologou, Katerina E. ; Amer, Dena A M ; Al-Hayani, Abdulmonem ; Ali El-Agnaf, Omar. / Elevated levels of cerebrospinal fluid α-synuclein oligomers in healthy asymptomatic LRRK2 mutation carriers. In: Frontiers in Aging Neuroscience. 2014 ; Vol. 6, No. SEP.
@article{26112763eff1445ea99c9ce036c8511a,
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. 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",
keywords = "Alpha-synuclien, Biomarkers, CSF, LRRK2 mutation carriers, Parkinson's disease",
author = "Aasly, {Jan O.} and Johansen, {Krisztina K.} and Gunnar Br{\o}nstad and War{\o}, {Bj{\o}rg J.} and Nour Majbour and Shiji Varghese and Fatimah Alzahmi and Paleologou, {Katerina E.} and Amer, {Dena A M} and Abdulmonem Al-Hayani and {Ali El-Agnaf}, Omar",
year = "2014",
doi = "10.3389/fnagi.2014.00248",
language = "English",
volume = "6",
journal = "Frontiers in Aging Neuroscience",
issn = "1663-4365",
publisher = "Frontiers Research Foundation",
number = "SEP",

}

TY - JOUR

T1 - Elevated levels of cerebrospinal fluid α-synuclein oligomers in healthy asymptomatic LRRK2 mutation carriers

AU - Aasly, Jan O.

AU - Johansen, Krisztina K.

AU - Brønstad, Gunnar

AU - Warø, Bjørg J.

AU - Majbour, Nour

AU - Varghese, Shiji

AU - Alzahmi, Fatimah

AU - Paleologou, Katerina E.

AU - Amer, Dena A M

AU - Al-Hayani, Abdulmonem

AU - Ali El-Agnaf, Omar

PY - 2014

Y1 - 2014

N2 - 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

AB - 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

KW - Alpha-synuclien

KW - Biomarkers

KW - CSF

KW - LRRK2 mutation carriers

KW - Parkinson's disease

UR - http://www.scopus.com/inward/record.url?scp=84907162800&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84907162800&partnerID=8YFLogxK

U2 - 10.3389/fnagi.2014.00248

DO - 10.3389/fnagi.2014.00248

M3 - Article

VL - 6

JO - Frontiers in Aging Neuroscience

JF - Frontiers in Aging Neuroscience

SN - 1663-4365

IS - SEP

M1 - 248

ER -