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ObjectiveWe 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.MethodsIn 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.ResultsWe observed a stepwise increase in symptoms across groups from HC to iOD to DLB, measured by MoCA (p 2 = 0.605).ConclusionsThese findings delineate the Lewy body symptom profile in iOD positioning iOD as a prodromal stage in which peripheral αSyn aggregation kinetics can be detected.
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