Abstract

Objective: Parkinson’s disease (PD) has significant clinical overlaps with atypical parkinsonism syndromes (APS), which have a poorer treatment response and a more aggressive course than PD. We aimed to identify plasma biomarkers to differentiate PD from APS.Methods: Plasma samples (n = 204) were obtained from healthy controls and from patients with PD, dementia with Lewy bodies (DLB), multiple system atrophy, progressive supranuclear palsy (PSP), corticobasal degeneration (CBD), or frontotemporal dementia (FTD) with parkinsonism (FTD-P) or without parkinsonism. We measured plasma levels of α-synuclein, total tau, p-Tau181, and amyloid beta 42 (Aβ42) by immunomagnetic reduction-based immunoassay.Results: Plasma α-synuclein level was significantly increased in patients with PD and APS when compared with controls and FTD without parkinsonism (p < 0.01). Total tau and p-Tau181 were significantly increased in all disease groups compared to controls, especially in patients with FTD (p < 0.01). A multivariate and receiver operating characteristic curve analysis revealed that a cut-off value for Aβ42 multiplied by p-Tau181 for discriminating patients with FTD from patients with PD and APS was 92.66 (pg/ml)2, with an area under the curve (AUC) of 0.932. An α-synuclein cut-off of 0.1977 pg/ml could separate FTD-P from FTD without parkinsonism (AUC 0.947). In patients with predominant parkinsonism, an α-synuclein cut-off of 1.388 pg/ml differentiated patients with PD from those with APS (AUC 0.87).Conclusion: Our results suggest that integrated plasma biomarkers improve the differential diagnosis of PD from APS (PSP, CBD, DLB, and FTD-P).

Highlights

  • Atypical parkinsonism syndrome (APS), including multiple system atrophy (MSA), progressive supranuclear palsy (PSP), corticobasal degeneration (CBD), dementia with Lewy body (DLB), and frontotemporal dementia (FTD) with parkinsonism (FTD-P), have a large clinical overlap with Parkinson’s disease (PD)

  • Patients with FTD combined with parkinsonism or not were younger than PD and other parkinsonian patients (PSP, CBD, and MSA) (p < 0.01 by Kruskal–Wallis test)

  • The Mini-Mental State Examination (MMSE) scores were significantly lower in patients in the PDD and FTD groups compared to other groups and controls (p < 0.01 by Kruskal–Wallis test)

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Summary

Methods

We measured plasma levels of α-synuclein, total tau, p-Tau181, and amyloid beta 42 (Aβ42) by immunomagnetic reduction-based immunoassay

Results
INTRODUCTION
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