Two-step detection of Lewy body pathology via smell-function testing and CSF α-synuclein seed amplification
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.
Authors
- Lyduine E. Collij (ORCID: https://orcid.org/0000-0001-6263-1762)
- Piero Parchi (ORCID: https://orcid.org/0000-0002-9444-9524)
- Sebastian Palmqvist (ORCID: https://orcid.org/0000-0002-9267-1930)
- Rik Ossenkoppele (ORCID: https://orcid.org/0000-0003-1584-7477)
- Charles H. Adler (ORCID: https://orcid.org/0000-0002-1045-2743)
- Sophie E Mastenbroek (ORCID: https://orcid.org/0009-0006-2759-9588)
- Oskar Hansson (ORCID: https://orcid.org/0000-0001-8467-7286)
- Geidy E. Serrano (ORCID: https://orcid.org/0000-0002-9527-2011)
- Frederik Barkhof (ORCID: https://orcid.org/0000-0003-3543-3706)
- Thomas G. Beach (ORCID: https://orcid.org/0000-0003-3296-6128)
- Jacob W. Vogel (ORCID: https://orcid.org/0000-0001-6394-9940)
- Claudia Marina Vargiu
- Serena Caldera
Institutions
- Lund University (SE)
- Science for Life Laboratory (SE)
- Amsterdam Neuroscience (NL)
- Istituto delle Scienze Neurologiche di Bologna (IT)
- Mayo Clinic in Arizona (US)
- Skåne University Hospital (SE)
- Banner Sun Health Research Institute (US)
- Amsterdam University Medical Centers (NL)
- Istituti di Ricovero e Cura a Carattere Scientifico (IT)
- University College London (GB)
- Vrije Universiteit Amsterdam (NL)
- Amsterdam UMC Location Vrije Universiteit Amsterdam (NL)
- University of Bologna (IT)
Publication Details
- Journal
- Nature Communications
- Published
- 2025-08-05
- DOI
- https://doi.org/10.1038/s41467-025-62458-7
- Citations
- 1
- Primary Topic
- Parkinson's Disease Mechanisms and Treatments
- Type
- article
- Field-Weighted Citation Impact
- 1.39
Funders
- Lunds Universitet