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Two-step detection of Lewy body pathology via smell-function testing and CSF α-synuclein seed amplification

Author

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  • Sophie E. Mastenbroek

    (Lund University
    Amsterdam University Medical Center location VUmc
    Amsterdam Neuroscience, Brain imaging)

  • Lyduine E. Collij

    (Lund University
    Amsterdam University Medical Center location VUmc
    Amsterdam Neuroscience, Brain imaging)

  • Jacob W. Vogel

    (Lund University)

  • Serena Caldera

    (IRCCS Istituto delle Scienze Neurologiche di Bologna)

  • Geidy E. Serrano

    (Banner Sun Health Research Institute)

  • Charles H. Adler

    (Mayo Clinic)

  • Claudia Marina Vargiu

    (IRCCS Istituto delle Scienze Neurologiche di Bologna)

  • Sebastian Palmqvist

    (Lund University
    Skåne University Hospital)

  • Frederik Barkhof

    (Amsterdam University Medical Center location VUmc
    Amsterdam Neuroscience, Brain imaging
    University College London)

  • Piero Parchi

    (IRCCS Istituto delle Scienze Neurologiche di Bologna
    University of Bologna)

  • Thomas G. Beach

    (Banner Sun Health Research Institute)

  • Rik Ossenkoppele

    (Lund University
    Vrije Universiteit Amsterdam, Amsterdam UMC location VUmc
    Amsterdam Neuroscience, Neurodegeneration)

  • Oskar Hansson

    (Lund University)

Abstract

Cerebrospinal fluid (CSF) α-synuclein (α-syn) seed amplification assays (SAAs) can detect Lewy body pathology (LBP) with high accuracy but are invasive and costly. To address these challenges, this study evaluated a two-step workflow combining prescreening via smell-function testing with confirmatory CSF α-syn SAA testing only in individuals with reduced smell, for predicting postmortem LBP status. Among 358 autopsied participants, the two-step workflow predicted brain LBP with high accuracy overall (94%), and within clinical subgroups (clinical parkinsonism=95%; clinical Alzheimer’s disease [AD]=94%; clinically unimpaired [CU]=93%). It reduced the need for confirmatory CSF testing by 43% overall (23% clinical parkinsonism; 35% clinical AD; 80% CU). In an independent in vivo cohort (N=1209), the workflow predicted CSF α-syn SAA status with 79% accuracy and reduced CSF testing by 26%. This approach may reduce invasive CSF testing, alleviating patient burden and lowering healthcare costs.

Suggested Citation

  • Sophie E. Mastenbroek & Lyduine E. Collij & Jacob W. Vogel & Serena Caldera & Geidy E. Serrano & Charles H. Adler & Claudia Marina Vargiu & Sebastian Palmqvist & Frederik Barkhof & Piero Parchi & Thom, 2025. "Two-step detection of Lewy body pathology via smell-function testing and CSF α-synuclein seed amplification," Nature Communications, Nature, vol. 16(1), pages 1-9, December.
    • Handle: RePEc:nat:natcom:v:16:y:2025:i:1:d:10.1038_s41467-025-62458-7
    DOI: 10.1038/s41467-025-62458-7
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