Abstract Details

Title Wide distribution of alpha-synuclein oligomers in multiple system atrophy brain detected by proximity ligation

Topic Movement Disorders

Presentation(s) P3 - Poster Session 3 (5:30 PM-6:30 PM)

Poster/Presentation
Number 10-010

Objective To reveal the distribution of alpha-synuclein (αS) oligomers as an early pathological change in multiple system atrophy (MSA) brains.

Background

The neuropathological hallmark of MSA is αS-positive glial cytoplasmic inclusions (GCIs). Although severe neuronal loss is also observed in MSA, neuronal inclusions (NIs) are rare compared to GCIs, such that the pathological mechanism of neuronal loss in MSA is unclear. GCIs and NIs are late-stage pathological features relative to αS oligomers and may not represent early changes in MSA. To reveal the early pathology of MSA, it is necessary to examine the early aggregation of αS, i.e., αS oligomers.

Design/Methods We adopted a proximity ligation assay (PLA) to examine the distribution of αS oligomers in brain tissue samples from patients with MSA and other diseases. This study included 5 MSA cases (age at death: 73.8 ± 8.3 years, disease duration: 9.0 ± 6.2 years), 5 Parkinson’s disease (PD) cases (age at death: 76.4 ± 6.3 years, disease duration: 11.6 ± 4.0 years) and 5 disease control cases (age at death: 63.6 ± 9.6 years, disease duration: 26.0 ± 15.5 years). As additional controls, post-mortem brain samples of 4 subjects without known neurological diseases (age at death: 63.3 ± 10.2 years) were used.

Results MSA brains showed a diffuse distribution and abundant accumulation of oligomeric αS in neurons as well as oligodendrocytes of the neocortex. In several regions, oligomeric αS signal intensity was higher in cases with MSA than in cases with PD. In contrast to previous studies, PLA revealed abundant αS oligomer accumulation in Purkinje cells in MSA brains, identifying oligomeric αS accumulation as a possible cause of Purkinje cell loss.

Conclusions The wide distribution of αS oligomers in MSA brain neurons has not been described previously and indicates a pathological mechanism of neuronal loss in MSA.

Authors/Disclosures
Hiroaki Sekiya, MD, PhD (Mayo Clinic) PRESENTER	Dr. Sekiya has nothing to disclose.
Hisatomo Kowa, MD, PhD (Kobe Univ Graduate School of Health Sciences)	No disclosure on file
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