Differential Circulating Levels of Naturally Occurring Antibody to α-Synuclein in Parkinson's Disease Dementia, Alzheimer's Disease, and Vascular Dementia.

Jian Wang,Mei Hu,Jian-Hong Wang,Shu Yang,Bo Zheng

doi:10.3389/fnagi.2020.571437

Abstract

Background: Aggregation of alpha-synuclein (α-Syn) is considered to be a significant pathological hallmark and a driving force of Parkinson’s disease (PD). PD dementia (PDD) occurs in a substantial number of PD patients. Naturally occurring antibody against α-Syn (NAb-α-Syn) exists ubiquitously in human blood and is reported to be altered in PD. However, it is not clear yet whether PDD had similar changes of circulating NAb-α-Syn.Methods: In this study, we recruited 61 PDD patients, 52 patients with Alzheimer’s disease (AD), 51 patients with vascular dementia (VaD), and 50 normal controls (NCs). ELISA was used to examine NAb-α-Syn levels in serum.Results: In comparison with NCs, serum levels of NAb-α-Syn were significantly lower in patients with PDD. However, serum levels of NAb-α-Syn were comparable among AD, VaD, and NC groups. Serum levels of NAb-α-Syn were positively correlated with the cognitive function, as reflected by Mini-Mental State Examination (MMSE) and Montreal Cognitive Assessment (MoCA). Serum levels of NAb-α-Syn were negatively correlated with the severity of PD [as reflected by the Unified Parkinson Disease Rating Scale (UPDRS)] and the duration of PD and PDD. Serum NAb-α-Syn can differentiate PDD patients from AD and VaD patients.Conclusion: These results suggest that circulating NAb-α-Syn might be a potential biomarker of PDD.

Highlights

Neurodegenerative disorders such as Parkinson’s disease (PD), Alzheimer’s disease (AD), and Creutzfeldt–Jakob disease (CJD) are characterized by the deposition and aggregation of misfolded proteins in the central nervous system (CNS; Skovronsky et al, 2006)
We investigated whether circulating NAb-α-Syn was capable of distinguishing PD dementia (PDD) from AD and vascular dementia (VaD)
The percentages of females were similar among groups (NC: 50.00%, PDD: 50.82%, AD: 48.08%, VaD: 47.06%; p = 0.978)

Summary

Introduction

Neurodegenerative disorders such as Parkinson’s disease (PD), Alzheimer’s disease (AD), and Creutzfeldt–Jakob disease (CJD) are characterized by the deposition and aggregation of misfolded proteins in the central nervous system (CNS; Skovronsky et al, 2006). After damage of neurons or axons, soluble α-Syn is released into the cerebral spinal fluid and efflux to the circulation in PD patients and in healthy individuals (El-Agnaf et al, 2006). This event may stimulate an induction of autoantibody formation against αSyn [naturally occurring antibody against α-Syn (NAb-αSyn); Papachroni et al, 2007]. Occurring antibody against α-Syn (NAb-α-Syn) exists ubiquitously in human blood and is reported to be altered in PD It is not clear yet whether PDD had similar changes of circulating NAb-α-Syn

Methods

Results

Conclusion