Mastenbroek, SophieE;
Collij, Lyduine E;
Vogel, Jacob W;
Caldera, Serena;
Serrano, Geidy E;
Adler, Charles H;
Vargiu, Claudia M;
... Hansson, Oskar; + view all
(2025)
Two-step detection of Lewy body pathology via smell-function testing and CSF α-synuclein seed amplification.
Nature Communications
, 16
, Article 7182. 10.1038/s41467-025-62458-7.
(In press).
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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.
| Type: | Article |
|---|---|
| Title: | Two-step detection of Lewy body pathology via smell-function testing and CSF α-synuclein seed amplification |
| Location: | England |
| Open access status: | An open access version is available from UCL Discovery |
| DOI: | 10.1038/s41467-025-62458-7 |
| Publisher version: | https://doi.org/10.1038/s41467-025-62458-7 |
| Language: | English |
| Additional information: | © The Author(s), 2025. This is an Open Access article distributed under the terms of the Creative Commons Attribution Licence (CC BY 4.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. https://creativecommons.org/licenses/by/4.0/ |
| Keywords: | Alzheimer's disease, Diagnostic markers, Movement disorders, Parkinson's disease. |
| UCL classification: | UCL UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences > UCL Queen Square Institute of Neurology |
| URI: | https://discovery.ucl.ac.uk/id/eprint/10212986 |
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