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

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.

Alpha-Synuclein in Peripheral Tissues as a Possible Marker for Neurological Diseases and Other Medical Conditions

“…Two studies showed similar serum/plasma aSyn levels in patients with DLB and controls [ 60 , 61 ], while another three showed increased [ 53 , 69 , 70 , 71 ] and decreased [ 70 ] aSyn in DLB patients. Concerning patients with PDD, three studies have shown increased serum/plasma aSyn [ 53 , 57 , 69 ], one study showed decreased aSyn [ 72 ], and another showed a lack of differences when compared with healthy controls [ 24 ]. Kronimus et al [ 73 ] described lower serum aSyn levels in patients with PDD compared with non-demented PD patients.…”

“…Several studies have shown similar serum aSyn levels [ 11 , 62 , 70 ] or antibodies against aSyn levels [ 20 , 69 , 72 ] in patients with Alzheimer’s disease (AD) [ 11 , 20 , 62 , 69 , 70 , 72 ] and similar serum aSyn antibodies levels in patients with vascular dementia [ 69 , 72 ] than those of healthy controls. In contrast, other studies described increased plasma aSyn levels in patients with AD compared with healthy controls [ 57 , 76 ], and another two studies showed increased autoantibodies against aSyn in AD patients [ 36 , 71 ], although fewer than those found in PD patients [ 71 ].…”