{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,22]],"date-time":"2026-09-22T04:43:27Z","timestamp":1790052207514,"version":"4.0.1"},"reference-count":0,"publisher":"Oxford University Press (OUP)","license":[{"start":{"date-parts":[[2026,5,19]],"date-time":"2026-05-19T00:00:00Z","timestamp":1779148800000},"content-version":"am","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>Parkinson\u2019s disease is characterized by the accumulation and propagation of \u03b1-synuclein pathology in the central nervous system, yet the contribution of peripheral \u03b1-synuclein sources remains unclear. Here, we identify erythrocytes as an important reservoir of \u03b1-synuclein and demonstrate that bone marrow-derived erythrocytic \u03b1-synuclein likely contributes to brain pathology and Parkinson\u2019s disease-related neurodegeneration.<\/jats:p>\n                  <jats:p>Using human tissues and mouse models, we show that erythrocytes harbour abundant \u03b1-synuclein species. Bone marrow transplantation revealed widespread distribution of bone marrow-derived \u03b1-synuclein in peripheral organs, with detectable but substantially lower levels in the brain. Within the central nervous system, bone marrow-derived \u03b1-synuclein preferentially accumulated in resident microglia, as confirmed by immunophenotyping and single-nucleus RNA sequencing, and was associated with microglial activation. Furthermore, erythrocyte-derived extracellular vesicles carrying \u03b1-synuclein can be readily taken up by microglia in vivo.<\/jats:p>\n                  <jats:p>Functionally, elevated levels of bone marrow-derived \u03b1-synuclein in the mouse brain resulted in dopaminergic dysfunction with a mild neurodegenerative phenotype under baseline conditions. Importantly, blood-brain barrier integrity critically regulated peripheral \u03b1-synuclein entry into the central nervous system. Disruption of the blood-brain barrier by endotoxin administration, mannitol treatment or focused ultrasound markedly increased the entry of peripheral \u03b1-synuclein into the brain, aggravating neurodegeneration and behavioural deficits.<\/jats:p>\n                  <jats:p>Collectively, these findings identify bone marrow-derived erythrocytic \u03b1-synuclein as a systemic contributor to the pathogenesis of Parkinson\u2019s disease and highlight blood-brain barrier integrity as a key permissive regulator of peripheral-to-central \u03b1-synuclein transmission.<\/jats:p>","DOI":"10.1093\/brain\/awag179","type":"journal-article","created":{"date-parts":[[2026,5,19]],"date-time":"2026-05-19T09:18:42Z","timestamp":1779182322000},"source":"Crossref","is-referenced-by-count":1,"title":["Parkinson\u2019s disease beyond the brain: erythrocyte \u03b1-synuclein transfer across the blood\u2013brain barrier"],"prefix":"10.1093","author":[{"given":"Ying","family":"Yang","sequence":"first","affiliation":[{"name":"Department of Pathology, the First Affiliated Hospital, Zhejiang University School of Medicine , Hangzhou, Zhejiang, 310003 ,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qi","family":"Liu","sequence":"additional","affiliation":[{"name":"Department of Pathology, the First Affiliated Hospital, Zhejiang University School of Medicine , Hangzhou, Zhejiang, 310003 ,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tao","family":"Zhou","sequence":"additional","affiliation":[{"name":"BGI Research , Hangzhou, Zhejiang, 310030 ,","place":["China"]},{"name":"College of Life Sciences, University of Chinese Academy of Sciences , Beijing, 100049 ,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jun","family":"Chen","sequence":"additional","affiliation":[{"name":"Department of Pathology, the First Affiliated Hospital, Zhejiang University School of Medicine , Hangzhou, Zhejiang, 310003 ,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wenjing","family":"Li","sequence":"additional","affiliation":[{"name":"School of Biomedical Engineering, ShanghaiTech University , Shanghai, 201210 ,","place":["China"]},{"name":"State Key Laboratory of Advanced Medical Materials and Devices, ShanghaiTech University , Shanghai, 201210 ,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wentao","family":"Chen","sequence":"additional","affiliation":[{"name":"Department of Pathology, the First Affiliated Hospital, Zhejiang University School of Medicine , Hangzhou, Zhejiang, 310003 ,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shaopeng","family":"Zeng","sequence":"additional","affiliation":[{"name":"Department of Pathology, the First Affiliated Hospital, Zhejiang University School of Medicine , Hangzhou, Zhejiang, 310003 ,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Huan","family":"Liu","sequence":"additional","affiliation":[{"name":"Department of Pathology, the First Affiliated Hospital, Zhejiang University School of Medicine , Hangzhou, Zhejiang, 310003 ,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6122-5209","authenticated-orcid":false,"given":"Pan","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Pathology, the First Affiliated Hospital, Zhejiang University School of Medicine , Hangzhou, Zhejiang, 310003 ,","place":["China"]},{"name":"National Human Brain Bank for Health and Disease, Zhejiang University , Hangzhou, Zhejiang, 310012 ,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Peizheng","family":"Yang","sequence":"additional","affiliation":[{"name":"Department of Pathology, the First Affiliated Hospital, Zhejiang University School of Medicine , Hangzhou, Zhejiang, 310003 ,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bin","family":"Xu","sequence":"additional","affiliation":[{"name":"Department of Pathology, the First Affiliated Hospital, Zhejiang University School of Medicine , Hangzhou, Zhejiang, 310003 ,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0019-619X","authenticated-orcid":false,"given":"Shiping","family":"Liu","sequence":"additional","affiliation":[{"name":"BGI Research , Hangzhou, Zhejiang, 310030 ,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiao","family":"Xiong","sequence":"additional","affiliation":[{"name":"Department of Pathology, the First Affiliated Hospital, Zhejiang University School of Medicine , Hangzhou, Zhejiang, 310003 ,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bingbing","family":"Cheng","sequence":"additional","affiliation":[{"name":"School of Biomedical Engineering, ShanghaiTech University , Shanghai, 201210 ,","place":["China"]},{"name":"State Key Laboratory of Advanced Medical Materials and Devices, ShanghaiTech University , Shanghai, 201210 ,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jing","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Pathology, the First Affiliated Hospital, Zhejiang University School of Medicine , Hangzhou, Zhejiang, 310003 ,","place":["China"]},{"name":"National Human Brain Bank for Health and Disease, Zhejiang University , Hangzhou, Zhejiang, 310012 ,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2026,5,19]]},"container-title":["Brain"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/academic.oup.com\/brain\/advance-article-pdf\/doi\/10.1093\/brain\/awag179\/68334034\/awag179.pdf","content-type":"application\/pdf","content-version":"am","intended-application":"syndication"},{"URL":"https:\/\/academic.oup.com\/brain\/advance-article-pdf\/doi\/10.1093\/brain\/awag179\/68334034\/awag179.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,5,19]],"date-time":"2026-05-19T09:18:43Z","timestamp":1779182323000},"score":1,"resource":{"primary":{"URL":"https:\/\/academic.oup.com\/brain\/advance-article\/doi\/10.1093\/brain\/awag179\/8687270"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,5,19]]},"references-count":0,"URL":"https:\/\/doi.org\/10.1093\/brain\/awag179","relation":{},"ISSN":["0006-8950","1460-2156"],"issn-type":[{"value":"0006-8950","type":"print"},{"value":"1460-2156","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,5,19]]},"article-number":"awag179"}}