# Correlating symptoms and skin α-synuclein seeding parameters in olfactory dysfunction and Lewy body dementia

## TL;DR

This study shows that individuals with olfactory dysfunction have early signs of α-synuclein aggregation linked to Lewy body dementia symptoms.

## Contribution

The study identifies olfactory dysfunction as a potential prodromal stage for Lewy body dementia with detectable peripheral α-synuclein aggregation.

## Key findings

- DLB patients showed accelerated α-synuclein seeding kinetics compared to iOD individuals.
- α-synuclein seeding parameters correlated with the number of DLB-related symptoms.
- iOD and DLB groups did not differ significantly in olfactory function but differed in symptom progression.

## Abstract

We investigated profiles of clinical symptoms and kinetic α-synuclein seed amplification assay (αSyn-SAA) parameters in skin across the spectrum of Lewy body disease by comparing normosmic healthy controls (HC), individuals with idiopathic olfactory dysfunction (iOD), and dementia with Lewy bodies (DLB) patients.

In this cross-sectional, case–control study, we included 49 αSyn-SAA-negative HC, 18 αSyn-SAA-positive iOD, and 25 αSyn-SAA-positive DLB patients. αSyn-SAA was performed on olfactory mucosa swabs and skin biopsies. Only the skin-derived kinetic parameters were explored for comparative kinetic analysis (13 iOD and 24 DLB). Clinical assessments included the Sniffin’ Sticks 16 for olfaction, Montreal Cognitive Assessment (MoCA), REM Sleep Behavior Disorder Single-Question (RBD1Q), and the Movement Disorder Society-Unified Parkinson’s Disease Rating Scale (MDS-UPDRS) I–III.

We observed a stepwise increase in symptoms across groups from HC to iOD to DLB, measured by MoCA (p < 0.05) and MDS-UPDRS I, II, III (p < 0.001). Participants with iOD and DLB did not differ in olfactory function (mean [SD]: 6.5 [2.4] vs. 6.0 [2.5], p = 0.51). Accelerated αSyn seeding kinetics, particularly shorter time to 50% of maximal fluorescence, were detected in DLB vs iOD (median hours [interquartile range] 17 [15–20] vs 14 [13–16], p = 0.017), achieving a classification accuracy of 74% (95% CI 57–91), and correlated with number of symptoms related to DLB without and with adjusting for age and sex (p = 0.002, R2 = 0.605).

These findings delineate the Lewy body symptom profile in iOD positioning iOD as a prodromal stage in which peripheral αSyn aggregation kinetics can be detected.

The online version contains supplementary material available at 10.1007/s00415-026-13745-w.