Pathological alpha-synuclein propagates through neural networks

184Citations
Citations of this article
244Readers
Mendeley users who have this article in their library.

This article is free to access.

Abstract

Background: α-Synuclein is the major component of filamentous inclusions that constitute the defining characteristic of Parkinson's disease, dementia with Lewy bodies and multiple system atrophy, so-called α-synucleinopathies. Recent studies revealed that intracerebral injection of recombinant α-synuclein fibrils into wild-type mouse brains induced prion-like propagation of hyperphosphorylated α-synuclein pathology. However, the propagation mechanisms of α-synuclein have not been fully elucidated. Results: In this study, in order to establish where and how α-synuclein pathology propagates, we injected recombinant mouse α-synuclein fibrils into three different brain areas (substantia nigra, striatum, and entorhinal cortex) of wild-type mice and compared the resulting distributions of α-synuclein pathology at 1 month after injection. Distinct patterns of pathology were observed in mice injected at the different sites. Within one month after injection, the pathology had spread to neurons in areas far from the injection sites, especially areas with direct neural connections to the injection sites. Surprisingly, phosphorylated tau and TDP-43 pathologies were also observed in mice injected with α-synuclein fibrils into striatum and entorhinal cortex at one month after injection. Phosphorylated tau and TDP-43 were accumulated in dot-like inclusions, but these were rarely colocalized with α-synuclein pathology. It seems that accumulation of α-synuclein has a synergistic effect on tau and TDP-43 aggregation. Additionally, intracerebral injection with sarkosyl-insoluble fraction prepared from wild-type mice injected synthetic α-synuclein fibrils can also induce phosphorylated α-synuclein pathology in wild-type mice. Conclusions: Our data indicate that α-synuclein aggregation spread by prion-like mechanisms through neural networks in mouse brains.

Cite

CITATION STYLE

APA

Masuda-Suzukake, M., Nonaka, T., Hosokawa, M., Kubo, M., Shimozawa, A., Akiyama, H., & Hasegawa, M. (2014, January 27). Pathological alpha-synuclein propagates through neural networks. Acta Neuropathologica Communications. BioMed Central Ltd. https://doi.org/10.1186/s40478-014-0088-8

Register to see more suggestions

Mendeley helps you to discover research relevant for your work.

Already have an account?

Save time finding and organizing research with Mendeley

Sign up for free