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TitleLack of pathogenic potential of peripheral α-synuclein aggregates from Parkinson's disease patients.
Publication TypeJournal Article
Year of Publication2018
AuthorsRecasens, Ariadna, Iria Carballo-Carbajal, Annabelle Parent, Jordi Bové, Ellen Gelpi, Eduardo Tolosa, and Miquel Vila
JournalActa Neuropathol Commun
Volume6
Issue1
Pagination8
Date Published2018 02 08
ISSN2051-5960
KeywordsAged, Aged, 80 and over, alpha-Synuclein, Alzheimer Disease, Animals, Brain, Female, Humans, Lewy Bodies, Male, Mice, Inbred C57BL, Parkinson Disease, Protein Aggregation, Pathological, Stellate Ganglion
Abstract

In Parkinson's disease (PD) there is widespread accumulation in the brain of abnormal α-synuclein aggregates forming intraneuronal Lewy bodies (LB). It is now well established that LB-type α-synuclein aggregates also occur in the peripheral autonomic nervous system in PD, from where it has been speculated they may progressively spread to the central nervous system through synaptically-connected brain networks and reach the substantia nigra to trigger herein dopaminergic dysfunction/degeneration and subsequent parkinsonism. Supporting a pathogenic role for α-synuclein aggregates we have previously shown that LB purified from postmortem PD brains promote α-synuclein pathology and dopaminergic neurodegeneration when intracerebrally inoculated into wild-type mice. However, the pathogenic capacity of PD-derived peripheral α-synuclein aggregates remains unknown. Here we addressed this question using purified LB-type α-synuclein aggregates from postmortem PD stellate ganglia (SG), a paravertebral sympathetic ganglion that exhibits consistent and conspicuous Lewy pathology in all PD patients. In contrast to our previous findings using nigral LB extracts, intracerebral inoculation of SG-derived LB into mice did not trigger long-term nigrostriatal neurodegeneration nor α-synuclein pathology. The differential pathogenic capacities of central- and peripheral-derived α-synuclein aggregates appear independent of the absolute amount and basic biochemical properties of α-synuclein within these aggregates and may rely instead on differences in α-synuclein conformation and/or yet unrecognized brain region-specific intrinsic factors. Our results argue against a putative pathogenic capacity of peripheral α-synuclein aggregates to promote α-synuclein pathology in the brain, propagate between neuronal networks or induce neurodegeneration.

DOI10.1186/s40478-018-0509-1
Alternate JournalActa Neuropathol Commun
PubMed ID29422109
PubMed Central IDPMC5806361
Grant ListPI13/01897 / / Instituto de Salud Carlos III / International
SAF2016- 77541-R / / Ministerio de Economía y Competitividad / International