The secondary structural difference between Lewy body and glial cytoplasmic inclusion in autopsy brain with synchrotron FTIR micro-spectroscopy

Katsuya Araki,Harutoshi Fujimura,Shigeo Murayama,Naoto Yagi,Yuka Ikemoto,Hideki Mochizuki,Hideki Hayakawa,Taro Moriwaki,Yoshitaka Nagai

doi:10.1038/s41598-020-76565-6

Abstract

Lewy bodies (LBs) and glial cytoplasmic inclusions (GCIs) are specific aggregates found in Parkinson’s disease (PD) and multiple system atrophy (MSA), respectively. These aggregates mainly consist of α-synuclein (α-syn) and have been reported to propagate in the brain. In animal experiments, the fibrils of α-syn propagate similarly to prions but there is still insufficient evidence to establish this finding in humans. Here, we analysed the protein structure of these aggregates in the autopsy brains of patients by synchrotron Fourier-transform infrared micro-spectroscopy (FTIRM) analysis without extracting or artificially amplifying the aggregates. As a result, we found that the content of the β-sheet structure in LBs in patients with PD was significantly higher than that in GCIs in patients with MSA (52.6 ± 1.9% in PD vs. 38.1 ± 0.9% in MSA, P < 0.001). These structural differences may provide clues to the differences in phenotypes of PD and MSA.

Highlights

By investigating the propagation of α-syn in the mouse brain using extracts from the brains of patients with Parkinson’s disease (PD) and multiple system atrophy (MSA), Prusiner et al have suggested the possibility that the human α-syn aggregates formed in the brains of patients with PD and MSA are structurally d ifferent[4]
To test this hypothesis, we performed synchrotron Fourier-transform infrared micro-spectroscopy (FTIRM) measurements of Lewy bodies (LBs) and glial cytoplasmic inclusions (GCIs) in the autopsy brains of patients pathologically diagnosed with PD and MSA, respectively
We studied brain sections that contained LBs and GCIs from four patients with PD and four with MSA (Supplementary Table S1)

Summary

Introduction

By investigating the propagation of α-syn in the mouse brain using extracts from the brains of patients with PD and MSA, Prusiner et al have suggested the possibility that the human α-syn aggregates formed in the brains of patients with PD and MSA are structurally d ifferent[4]. To test this hypothesis, we performed synchrotron FTIRM measurements of LBs and GCIs in the autopsy brains of patients pathologically diagnosed with PD and MSA, respectively. To the best of our knowledge, this is the first study in which aggregates in the brain were directly (without extraction or artificial amplification) analysed to confirm the secondary structural differences between α-syn aggregates

Methods

Results

Conclusion