{"entity": "publication", "iuid": "ea6d5d8e7dd44f16887f6ca07d58f0be", "timestamp": "2026-08-20T12:11:54.817Z", "links": {"self": {"href": "https://publications.scilifelab.se/publication/ea6d5d8e7dd44f16887f6ca07d58f0be.json"}, "display": {"href": "https://publications.scilifelab.se/publication/ea6d5d8e7dd44f16887f6ca07d58f0be"}}, "title": "Accumulation of alpha-synuclein within the liver, potential role in the clearance of brain pathology associated with Parkinson's disease.", "authors": [{"family": "Reyes", "given": "Juan F", "initials": "JF", "orcid": "0000-0002-6361-534X", "researcher": {"href": "https://publications.scilifelab.se/researcher/7fea61ce9b8b4255a5d19e13e9b503b8.json"}}, {"family": "Ekmark-L\u00e9wen", "given": "Sara", "initials": "S"}, {"family": "Perdiki", "given": "Marina", "initials": "M"}, {"family": "Klingstedt", "given": "Ther\u00e9se", "initials": "T"}, {"family": "Hoffmann", "given": "Alana", "initials": "A"}, {"family": "Wiechec", "given": "Emilia", "initials": "E"}, {"family": "Nilsson", "given": "Per", "initials": "P"}, {"family": "Nilsson", "given": "K Peter R", "initials": "KPR"}, {"family": "Alafuzoff", "given": "Irina", "initials": "I"}, {"family": "Ingelsson", "given": "Martin", "initials": "M"}, {"family": "Hallbeck", "given": "Martin", "initials": "M"}], "type": "journal article", "published": "2021-03-20", "journal": {"title": "Acta Neuropathol Commun", "issn": "2051-5960", "volume": "9", "issue": "1", "pages": "46", "issn-l": "2051-5960"}, "abstract": "Alpha-synuclein (\u03b1-syn) aggregation is the hallmark pathological lesion in brains of patients with Parkinson's disease (PD) and related neurological disorders characterized as synucleinopathies. Accumulating evidence now indicates that \u03b1-syn deposition is also present within the gut and other peripheral organs outside the central nervous system (CNS). In the current study, we demonstrate for the first time that \u03b1-syn pathology also accumulates within the liver, the main organ responsible for substance clearance and detoxification. We further demonstrate that cultured human hepatocytes readily internalize oligomeric \u03b1-syn assemblies mediated, at least in part, by the gap junction protein connexin-32 (Cx32). Moreover, we identified a time-dependent accumulation of \u03b1-syn within the liver of three different transgenic (tg) mouse models expressing human \u03b1-syn under CNS-specific promoters, despite the lack of \u03b1-syn mRNA expression within the liver. Such a brain-to-liver transmission route could be further corroborated by detection of \u03b1-syn pathology within the liver of wild type mice one month after a single striatal \u03b1-syn injection. In contrast to the synucleinopathy models, aged mice modeling AD rarely show any amyloid-beta (A\u00df) deposition within the liver. In human post-mortem liver tissue, we identified cases with neuropathologically confirmed \u03b1-syn pathology containing \u03b1-syn within hepatocellular structures to a higher degree (75%) than control subjects without \u03b1-syn accumulation in the brain (57%). Our results reveal that \u03b1-syn accumulates within the liver and may be derived from the brain or other peripheral sources. Collectively, our findings indicate that the liver may play a role in the clearance and detoxification of pathological proteins in PD and related synucleinopathies.", "doi": "10.1186/s40478-021-01136-3", "pmid": "33743820", "labels": [], "xrefs": [{"db": "pmc", "key": "PMC7980682"}, {"db": "pii", "key": "10.1186/s40478-021-01136-3"}], "notes": [], "created": "2026-08-18T09:05:40.106Z", "modified": "2026-08-18T09:05:40.216Z"}