α-Synuclein species as potential cerebrospinal fluid biomarkers for dementia with lewy bodies

Inger van Steenoven, Nour Majbour, Nishant Vaikath, Henk W. Berendse, Wiesje M. van der Flier, Wilma D.J. van de Berg, Charlotte E. Teunissen, Afina W. Lemstra, Omar Ali El-Agnaf

Research output: Contribution to journalArticle

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Abstract

Background: The objective of this study was to investigate the discriminating value of a range of CSF α-synuclein species for dementia with Lewy bodies compared with Alzheimer's disease, PD, and cognitively normal controls. Methods: We applied our recently published enzyme-linked immunosorbent assays to measure the CSF levels of total α-synuclein, oligomeric α-synuclein, and phosphorylated α-synuclein in dementia with Lewy bodies (n = 42), Alzheimer's disease (n = 39), PD (n = 46), and controls (n = 78). General linear models corrected for age and sex were performed to assess differences in α-synuclein levels between groups. We used backward-elimination logistic regression analysis to investigate the combined discriminating value of the different CSF α-synuclein species and Alzheimer's disease biomarkers. Results: CSF levels of total α-synuclein were lower in dementia with Lewy bodies and PD compared with Alzheimer's disease as well as controls (P < 0.001). In contrast, CSF levels of oligomeric α-synuclein were higher in dementia with Lewy bodies and PD compared with Alzheimer's disease (P < 0.05) and controls (P < 0.001). No group differences were found for phosphorylated α-synuclein. In dementia with Lewy bodies and PD, CSF total α-synuclein levels positively correlated with tau and phosphorylated tau (both r > 0.40, P < 0.01), but not with amyloid-β1-42. The optimal combination to differentiate dementia with Lewy bodies from controls consisted of amyloid-β1-42, tau, total α-synuclein, oligomeric α-synuclein, age, and sex (AUC, 0.90). To differentiate dementia with Lewy bodies from Alzheimer's disease, the combination of tau and oligomeric α-synuclein resulted in an AUC of 0.83. CSF α-synuclein species do not contribute to the differentiation of dementia with Lewy bodies from PD. Conclusions: CSF α-synuclein species could be useful as part of a biomarker panel for dementia with Lewy bodies. Evaluating both oligomeric α-synuclein and total α-synuclein in CSF helps in the diagnosis of dementia with Lewy bodies.

Original languageEnglish
JournalMovement Disorders
DOIs
Publication statusAccepted/In press - 1 Jan 2018

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Synucleins
Lewy Body Disease
Cerebrospinal Fluid
Biomarkers
Alzheimer Disease
Amyloid
Area Under Curve

Keywords

  • biomarkers
  • CSF
  • dementia with Lewy bodies
  • α-synuclein

ASJC Scopus subject areas

  • Neurology
  • Clinical Neurology

Cite this

α-Synuclein species as potential cerebrospinal fluid biomarkers for dementia with lewy bodies. / van Steenoven, Inger; Majbour, Nour; Vaikath, Nishant; Berendse, Henk W.; van der Flier, Wiesje M.; van de Berg, Wilma D.J.; Teunissen, Charlotte E.; Lemstra, Afina W.; Ali El-Agnaf, Omar.

In: Movement Disorders, 01.01.2018.

Research output: Contribution to journalArticle

van Steenoven, Inger ; Majbour, Nour ; Vaikath, Nishant ; Berendse, Henk W. ; van der Flier, Wiesje M. ; van de Berg, Wilma D.J. ; Teunissen, Charlotte E. ; Lemstra, Afina W. ; Ali El-Agnaf, Omar. / α-Synuclein species as potential cerebrospinal fluid biomarkers for dementia with lewy bodies. In: Movement Disorders. 2018.
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AU - Vaikath, Nishant

AU - Berendse, Henk W.

AU - van der Flier, Wiesje M.

AU - van de Berg, Wilma D.J.

AU - Teunissen, Charlotte E.

AU - Lemstra, Afina W.

AU - Ali El-Agnaf, Omar

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N2 - Background: The objective of this study was to investigate the discriminating value of a range of CSF α-synuclein species for dementia with Lewy bodies compared with Alzheimer's disease, PD, and cognitively normal controls. Methods: We applied our recently published enzyme-linked immunosorbent assays to measure the CSF levels of total α-synuclein, oligomeric α-synuclein, and phosphorylated α-synuclein in dementia with Lewy bodies (n = 42), Alzheimer's disease (n = 39), PD (n = 46), and controls (n = 78). General linear models corrected for age and sex were performed to assess differences in α-synuclein levels between groups. We used backward-elimination logistic regression analysis to investigate the combined discriminating value of the different CSF α-synuclein species and Alzheimer's disease biomarkers. Results: CSF levels of total α-synuclein were lower in dementia with Lewy bodies and PD compared with Alzheimer's disease as well as controls (P < 0.001). In contrast, CSF levels of oligomeric α-synuclein were higher in dementia with Lewy bodies and PD compared with Alzheimer's disease (P < 0.05) and controls (P < 0.001). No group differences were found for phosphorylated α-synuclein. In dementia with Lewy bodies and PD, CSF total α-synuclein levels positively correlated with tau and phosphorylated tau (both r > 0.40, P < 0.01), but not with amyloid-β1-42. The optimal combination to differentiate dementia with Lewy bodies from controls consisted of amyloid-β1-42, tau, total α-synuclein, oligomeric α-synuclein, age, and sex (AUC, 0.90). To differentiate dementia with Lewy bodies from Alzheimer's disease, the combination of tau and oligomeric α-synuclein resulted in an AUC of 0.83. CSF α-synuclein species do not contribute to the differentiation of dementia with Lewy bodies from PD. Conclusions: CSF α-synuclein species could be useful as part of a biomarker panel for dementia with Lewy bodies. Evaluating both oligomeric α-synuclein and total α-synuclein in CSF helps in the diagnosis of dementia with Lewy bodies.

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