| Title: |
Two-step detection of Lewy body pathology via smell-function testing and CSF α-synuclein seed amplification |
| Authors: |
Mastenbroek S. E.; Collij L. E.; Vogel J. W.; Caldera S.; Serrano G. E.; Adler C. H.; Vargiu C. M.; Palmqvist S.; Barkhof F.; Parchi P.; Beach T. G.; Ossenkoppele R.; Hansson O. |
| Contributors: |
Mastenbroek, S. E.; Collij, L. E.; Vogel, J. W.; Caldera, S.; Serrano, G. E.; Adler, C. H.; Vargiu, C. M.; Palmqvist, S.; Barkhof, F.; Parchi, P.; Beach, T. G.; Ossenkoppele, R.; Hansson, O. |
| Publication Year: |
2025 |
| Collection: |
IRIS Università degli Studi di Bologna (CRIS - Current Research Information System) |
| Subject Terms: |
Synuclein; SAA; RT-QuIC; smell; biomarkers; preclinical; Lewy body disease |
| Description: |
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. |
| Document Type: |
article in journal/newspaper |
| File Description: |
ELETTRONICO |
| Language: |
English |
| Relation: |
info:eu-repo/semantics/altIdentifier/pmid/40764485; info:eu-repo/semantics/altIdentifier/wos/WOS:001545534800041; volume:16; issue:1; firstpage:1; lastpage:9; numberofpages:9; journal:NATURE COMMUNICATIONS; https://hdl.handle.net/11585/1039110 |
| DOI: |
10.1038/s41467-025-62458-7 |
| Availability: |
https://hdl.handle.net/11585/1039110; https://doi.org/10.1038/s41467-025-62458-7; https://www.nature.com/articles/s41467-025-62458-7 |
| Rights: |
info:eu-repo/semantics/openAccess ; license:Licenza per Accesso Aperto. Creative Commons Attribuzione (CCBY) ; license uri:iris.PUB15 |
| Accession Number: |
edsbas.AF0052D6 |
| Database: |
BASE |