Session Time: 1:15pm-2:45pm
Location: Les Muses, Level 3
Objective: To examine the distribution of alpha-synuclein (αSyn) oligomers as an early pathological change in multiple system atrophy (MSA) brains.
Background: Although severe neuronal loss is observed in MSA, neuronal inclusions (NIs) are rare compared to αSyn-positive glial cytoplasmic inclusions (GCIs), such that the pathological mechanism of neuronal loss in MSA is unclear. GCIs and NIs are late-stage pathological features relative to αSyn oligomers and may not represent early changes. To reveal the early pathology of MSA, it is necessary to examine the early aggregation of αSyn, i.e., αSyn oligomers.
Method: We adopted a proximity ligation assay (PLA) to examine the distribution of αSyn oligomers in brain samples from patients with MSA and other diseases. We examined 5 MSA cases, 5 Parkinson’s disease (PD) cases, and 9 control cases. We expanded the regions of analysis to neocortex and hippocampus, as well as the striatum and brain stem.
Results: MSA brains showed a wide distribution and abundant accumulation of oligomeric αSyn in neurons as well as oligodendrocytes of the neocortex, which was largely unique to MSA. In the MSA group, 4 of 5 cases showed clustered staining in neurons of 9 cortical regions, whereas such staining was not observed in PD or control cases, except in 2 regions of 2 PD cases. In the cerebellum, abundant αSyn oligomer was also observed in Purkinje cells of MSA brains. In addition to the neuronal staining, diffuse neuropil staining was detected in MSA cases. The αSyn-PLA intensity was significantly higher in several cortical regions in patients with MSA than in patients with PD. In canonical regions of MSA such as putamen, substantia nigra, pontine nucleus and inferior olivary nucleus, neuronal staining was relatively unremarkable and the severity of αSyn-PLA in neuropils was relatively low. We observed a significant inverse correlation of neuronal loss and αSyn-PLA severity in these areas.
Conclusion: We visualized αSyn oligomers using a PLA approach and showed a wide distribution of αSyn oligomers in neurons of MSA. Considering the aggregation process of αSyn and the toxicity of αSyn oligomers, our study suggests that αSyn oligomer-mediated toxicity is an early pathological event in MSA and that the primary lesion of MSA may lie in neurons.
To cite this abstract in AMA style:H. Sekiya, H. Kowa, H. Koga, M. Takata, W. Satake, N. Futamura, I. Funakawa, K. Jinnai, M. Kanagawa, K. Kobayashi, T. Toda. Widespread distribution and abundant accumulation of alpha-synuclein oligomers in multiple system atrophy brain [abstract]. Mov Disord. 2019; 34 (suppl 2). https://www.mdsabstracts.org/abstract/widespread-distribution-and-abundant-accumulation-of-alpha-synuclein-oligomers-in-multiple-system-atrophy-brain/. Accessed December 6, 2023.
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MDS Abstracts - https://www.mdsabstracts.org/abstract/widespread-distribution-and-abundant-accumulation-of-alpha-synuclein-oligomers-in-multiple-system-atrophy-brain/