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CSF proteome profiling reveals biomarkers to discriminate dementia with Lewy bodies from Alzheimer´s disease

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Listed:
  • Marta Campo

    (Amsterdam University Medical Centers, Location VUmc
    Barcelonaßeta Brain Research Center, Pasqual Maragall Foundation
    Universidad San Pablo-CEU, CEU Universities)

  • Lisa Vermunt

    (Amsterdam University Medical Centers, Location VUmc
    Amsterdam University Medical Centers, Location VUmc)

  • Carel F. W. Peeters

    (Wageningen University & Research)

  • Anne Sieben

    (Antwerp University)

  • Yanaika S. Hok-A-Hin

    (Amsterdam University Medical Centers, Location VUmc)

  • Alberto Lleó

    (Institut d’Investigacions Biomèdiques Sant Pau (IIB SANT PAU) - Hospital de Sant Pau, Universitat Autònoma de Barcelona, Hospital de la Santa Creu i Sant Pau
    Center of Biomedical Investigation Network for Neurodegenerative Diseases (CIBERNED))

  • Daniel Alcolea

    (Institut d’Investigacions Biomèdiques Sant Pau (IIB SANT PAU) - Hospital de Sant Pau, Universitat Autònoma de Barcelona, Hospital de la Santa Creu i Sant Pau
    Center of Biomedical Investigation Network for Neurodegenerative Diseases (CIBERNED))

  • Mirrelijn Nee

    (Amsterdam University Medical Centers, Location VUmc)

  • Sebastiaan Engelborghs

    (University of Antwerp
    Vrije Universiteit Brussel, Center for Neurosciences (C4N), Neuroprotection and Neuromodulation Research Group (NEUR)
    Universitair Ziekenhuis Brussel, Department of Neurology)

  • Juliette L. Alphen

    (Amsterdam University Medical Centers, Location VUmc)

  • Sanaz Arezoumandan

    (University of Pennsylvania)

  • Alice Chen-Plotkin

    (University of Pennsylvania)

  • David J. Irwin

    (University of Pennsylvania)

  • Wiesje M. Flier

    (Amsterdam University Medical Centers, Location VUmc
    Amsterdam University Medical Centers, Location VUmc)

  • Afina W. Lemstra

    (Amsterdam University Medical Centers, Location VUmc)

  • Charlotte E. Teunissen

    (Amsterdam University Medical Centers, Location VUmc)

Abstract

Diagnosis of dementia with Lewy bodies (DLB) is challenging and specific biofluid biomarkers are highly needed. We employed proximity extension-based assays to measure 665 proteins in the cerebrospinal fluid (CSF) from patients with DLB (n = 109), Alzheimer´s disease (AD, n = 235) and cognitively unimpaired controls (n = 190). We identified over 50 CSF proteins dysregulated in DLB, enriched in myelination processes among others. The dopamine biosynthesis enzyme DDC was the strongest dysregulated protein, and could efficiently discriminate DLB from controls and AD (AUC:0.91 and 0.81 respectively). Classification modeling unveiled a 7-CSF biomarker panel that better discriminate DLB from AD (AUC:0.93). A custom multiplex panel for six of these markers (DDC, CRH, MMP-3, ABL1, MMP-10, THOP1) was developed and validated in independent cohorts, including an AD and DLB autopsy cohort. This DLB CSF proteome study identifies DLB-specific protein changes and translates these findings to a practicable biomarker panel that accurately identifies DLB patients, providing promising diagnostic and clinical trial testing opportunities.

Suggested Citation

  • Marta Campo & Lisa Vermunt & Carel F. W. Peeters & Anne Sieben & Yanaika S. Hok-A-Hin & Alberto Lleó & Daniel Alcolea & Mirrelijn Nee & Sebastiaan Engelborghs & Juliette L. Alphen & Sanaz Arezoumandan, 2023. "CSF proteome profiling reveals biomarkers to discriminate dementia with Lewy bodies from Alzheimer´s disease," Nature Communications, Nature, vol. 14(1), pages 1-14, December.
    • Handle: RePEc:nat:natcom:v:14:y:2023:i:1:d:10.1038_s41467-023-41122-y
    DOI: 10.1038/s41467-023-41122-y
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    References listed on IDEAS

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