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Original Contribution

Plasma Aβ (Amyloid-β) Levels and Severity and Progression of Small Vessel Disease

Esther M.C. van Leijsen, H. Bea Kuiperij, Iris Kersten, Mayra I. Bergkamp, Ingeborg W.M. van Uden, Hugo Vanderstichele, Erik Stoops, Jurgen A.H.R. Claassen, Ewoud J. van Dijk, Frank-Erik de Leeuw, Marcel M. Verbeek
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https://doi.org/10.1161/STROKEAHA.117.019810
Stroke. 2018;49:884-890
Originally published March 14, 2018
Esther M.C. van Leijsen
From the Department of Neurology (E.M.C.v.L., H.B.K., I.K., M.I.B., I.W.M.v.U., E.J.v.D., F.-E.d.L., M.M.V.), Department of Laboratory Medicine (H.B.K., I.K., M.M.V.), and Department of Geriatric Medicine (J.A.H.R.C.), Donders Institute for Brain, Cognition and Behaviour, Donders Center for Medical Neuroscience, Radboud University Medical Center, Nijmegen, the Netherlands; and ADx NeuroSciences, Ghent, Belgium (H.V., E.S.).
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H. Bea Kuiperij
From the Department of Neurology (E.M.C.v.L., H.B.K., I.K., M.I.B., I.W.M.v.U., E.J.v.D., F.-E.d.L., M.M.V.), Department of Laboratory Medicine (H.B.K., I.K., M.M.V.), and Department of Geriatric Medicine (J.A.H.R.C.), Donders Institute for Brain, Cognition and Behaviour, Donders Center for Medical Neuroscience, Radboud University Medical Center, Nijmegen, the Netherlands; and ADx NeuroSciences, Ghent, Belgium (H.V., E.S.).
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Iris Kersten
From the Department of Neurology (E.M.C.v.L., H.B.K., I.K., M.I.B., I.W.M.v.U., E.J.v.D., F.-E.d.L., M.M.V.), Department of Laboratory Medicine (H.B.K., I.K., M.M.V.), and Department of Geriatric Medicine (J.A.H.R.C.), Donders Institute for Brain, Cognition and Behaviour, Donders Center for Medical Neuroscience, Radboud University Medical Center, Nijmegen, the Netherlands; and ADx NeuroSciences, Ghent, Belgium (H.V., E.S.).
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Mayra I. Bergkamp
From the Department of Neurology (E.M.C.v.L., H.B.K., I.K., M.I.B., I.W.M.v.U., E.J.v.D., F.-E.d.L., M.M.V.), Department of Laboratory Medicine (H.B.K., I.K., M.M.V.), and Department of Geriatric Medicine (J.A.H.R.C.), Donders Institute for Brain, Cognition and Behaviour, Donders Center for Medical Neuroscience, Radboud University Medical Center, Nijmegen, the Netherlands; and ADx NeuroSciences, Ghent, Belgium (H.V., E.S.).
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Ingeborg W.M. van Uden
From the Department of Neurology (E.M.C.v.L., H.B.K., I.K., M.I.B., I.W.M.v.U., E.J.v.D., F.-E.d.L., M.M.V.), Department of Laboratory Medicine (H.B.K., I.K., M.M.V.), and Department of Geriatric Medicine (J.A.H.R.C.), Donders Institute for Brain, Cognition and Behaviour, Donders Center for Medical Neuroscience, Radboud University Medical Center, Nijmegen, the Netherlands; and ADx NeuroSciences, Ghent, Belgium (H.V., E.S.).
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Hugo Vanderstichele
From the Department of Neurology (E.M.C.v.L., H.B.K., I.K., M.I.B., I.W.M.v.U., E.J.v.D., F.-E.d.L., M.M.V.), Department of Laboratory Medicine (H.B.K., I.K., M.M.V.), and Department of Geriatric Medicine (J.A.H.R.C.), Donders Institute for Brain, Cognition and Behaviour, Donders Center for Medical Neuroscience, Radboud University Medical Center, Nijmegen, the Netherlands; and ADx NeuroSciences, Ghent, Belgium (H.V., E.S.).
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Erik Stoops
From the Department of Neurology (E.M.C.v.L., H.B.K., I.K., M.I.B., I.W.M.v.U., E.J.v.D., F.-E.d.L., M.M.V.), Department of Laboratory Medicine (H.B.K., I.K., M.M.V.), and Department of Geriatric Medicine (J.A.H.R.C.), Donders Institute for Brain, Cognition and Behaviour, Donders Center for Medical Neuroscience, Radboud University Medical Center, Nijmegen, the Netherlands; and ADx NeuroSciences, Ghent, Belgium (H.V., E.S.).
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Jurgen A.H.R. Claassen
From the Department of Neurology (E.M.C.v.L., H.B.K., I.K., M.I.B., I.W.M.v.U., E.J.v.D., F.-E.d.L., M.M.V.), Department of Laboratory Medicine (H.B.K., I.K., M.M.V.), and Department of Geriatric Medicine (J.A.H.R.C.), Donders Institute for Brain, Cognition and Behaviour, Donders Center for Medical Neuroscience, Radboud University Medical Center, Nijmegen, the Netherlands; and ADx NeuroSciences, Ghent, Belgium (H.V., E.S.).
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Ewoud J. van Dijk
From the Department of Neurology (E.M.C.v.L., H.B.K., I.K., M.I.B., I.W.M.v.U., E.J.v.D., F.-E.d.L., M.M.V.), Department of Laboratory Medicine (H.B.K., I.K., M.M.V.), and Department of Geriatric Medicine (J.A.H.R.C.), Donders Institute for Brain, Cognition and Behaviour, Donders Center for Medical Neuroscience, Radboud University Medical Center, Nijmegen, the Netherlands; and ADx NeuroSciences, Ghent, Belgium (H.V., E.S.).
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Frank-Erik de Leeuw
From the Department of Neurology (E.M.C.v.L., H.B.K., I.K., M.I.B., I.W.M.v.U., E.J.v.D., F.-E.d.L., M.M.V.), Department of Laboratory Medicine (H.B.K., I.K., M.M.V.), and Department of Geriatric Medicine (J.A.H.R.C.), Donders Institute for Brain, Cognition and Behaviour, Donders Center for Medical Neuroscience, Radboud University Medical Center, Nijmegen, the Netherlands; and ADx NeuroSciences, Ghent, Belgium (H.V., E.S.).
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Marcel M. Verbeek
From the Department of Neurology (E.M.C.v.L., H.B.K., I.K., M.I.B., I.W.M.v.U., E.J.v.D., F.-E.d.L., M.M.V.), Department of Laboratory Medicine (H.B.K., I.K., M.M.V.), and Department of Geriatric Medicine (J.A.H.R.C.), Donders Institute for Brain, Cognition and Behaviour, Donders Center for Medical Neuroscience, Radboud University Medical Center, Nijmegen, the Netherlands; and ADx NeuroSciences, Ghent, Belgium (H.V., E.S.).
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Abstract

Background and Purpose—Cerebral small vessel disease (SVD) is a frequent pathology in aging and contributor to the development of dementia. Plasma Aβ (amyloid β) levels may be useful as early biomarker, but the role of plasma Aβ in SVD remains to be elucidated. We investigated the association of plasma Aβ levels with severity and progression of SVD markers.

Methods—We studied 487 participants from the RUN DMC study (Radboud University Nijmegen Diffusion Tensor and Magnetic Resonance Imaging Cohort) of whom 258 participants underwent 3 MRI assessments during 9 years. We determined baseline plasma Aβ38, Aβ40, and Aβ42 levels using ELISAs. We longitudinally assessed volume of white matter hyperintensities semiautomatically and manually rated lacunes and microbleeds. We analyzed associations between plasma Aβ and SVD markers by ANCOVA adjusted for age, sex, and hypertension.

Results—Cross-sectionally, plasma Aβ40 levels were elevated in participants with microbleeds (mean, 205.4 versus 186.4 pg/mL; P<0.01) and lacunes (mean, 194.8 versus 181.2 pg/mL; P<0.05). Both Aβ38 and Aβ40 were elevated in participants with severe white matter hyperintensities (Aβ38, 25.3 versus 22.7 pg/mL; P<0.01; Aβ40, 201.8 versus 183.3 pg/mL; P<0.05). Longitudinally, plasma Aβ40 levels were elevated in participants with white matter hyperintensity progression (mean, 194.6 versus 182.9 pg/mL; P<0.05). Both Aβ38 and Aβ40 were elevated in participants with incident lacunes (Aβ38, 24.5 versus 22.5 pg/mL; P<0.05; Aβ40, 194.9 versus 181.2 pg/mL; P<0.01) and Aβ42 in participants with incident microbleeds (62.8 versus 60.4 pg/mL; P<0.05).

Conclusions—Plasma Aβ levels are associated with both presence and progression of SVD markers, suggesting that Aβ pathology might contribute to the development and progression of SVD. Plasma Aβ levels might thereby serve as inexpensive and noninvasive measure for identifying individuals with increased risk for progression of SVD.

  • amyloid
  • cerebral small vessel diseases
  • humans
  • neuroimaging
  • white matter
  • Received October 19, 2017.
  • Revision received January 10, 2018.
  • Accepted February 5, 2018.
  • © 2018 American Heart Association, Inc.
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    Plasma Aβ (Amyloid-β) Levels and Severity and Progression of Small Vessel Disease
    Esther M.C. van Leijsen, H. Bea Kuiperij, Iris Kersten, Mayra I. Bergkamp, Ingeborg W.M. van Uden, Hugo Vanderstichele, Erik Stoops, Jurgen A.H.R. Claassen, Ewoud J. van Dijk, Frank-Erik de Leeuw and Marcel M. Verbeek
    Stroke. 2018;49:884-890, originally published March 14, 2018
    https://doi.org/10.1161/STROKEAHA.117.019810

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    Plasma Aβ (Amyloid-β) Levels and Severity and Progression of Small Vessel Disease
    Esther M.C. van Leijsen, H. Bea Kuiperij, Iris Kersten, Mayra I. Bergkamp, Ingeborg W.M. van Uden, Hugo Vanderstichele, Erik Stoops, Jurgen A.H.R. Claassen, Ewoud J. van Dijk, Frank-Erik de Leeuw and Marcel M. Verbeek
    Stroke. 2018;49:884-890, originally published March 14, 2018
    https://doi.org/10.1161/STROKEAHA.117.019810
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