Objective: To examine the distribution of alpha-synuclein (αSYN) oligomers in Parkinson’s disease (PD) brains and compare the distribution of αSYN oligomers and Lewy bodies.

Background: Lewy bodies, the late-stage αSYN aggregation, have been considered as the pathological hallmark of PD. However, the presence of incidental Lewy bodies in elderly individuals without Parkinsonism and the absence of Lewy bodies in some of the familial PD patients with Parkinsonism have been reported. Whether Lewy bodies drive neurodegeneration remains controversial and αSYN oligomers, the early-stage αSYN aggregation, may play the pathogenic role.

Method: We examined autopsied brains from 5 PD patients and 9 control cases. We conducted phosphorylated-αSYN immunostaining to detect Lewy bodies and adopted a proximity ligation assay (PLA) to examine the distribution of αSYN oligomers.

Results: As well as the punctate staining in remaining neurons in the substantia nigra, PD patients showed widespread αSYN-PLA signals in the putamen, pontine nuclei, and the frontal cortex, whereas such signals were rarely found in control cases. Among PD patients, the Braak stage was 3 in 2 patients, 5 in 1 patient, and 6 in 2 patients. In αSYN-PLA staining, Lewy bodies themselves were not stained and the punctate signal was found in the periphery of Lewy bodies. We found punctate staining of αSYN oligomers in cortical neurons even in patients with Braak stage 3, who showed no Lewy bodies in cortical neurons.

Conclusion: We found a widespread distribution of αSYN oligomers in PD brains. The distribution of αSYN oligomers was more widespread than that of Lewy bodies. The formation of αSYN oligomers may precede the formation of Lewy bodies and αSYN oligomers may distribute widely throughout the brain even in the earlier course of PD.

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MDS Abstracts - https://www.mdsabstracts.org/abstract/difference-in-distribution-between-alpha-synuclein-oligomers-and-lewy-bodies-in-parkinsons-disease-brain/