{
  "abstract": "Parkinson’s disease (PD) exhibits a characteristic posterior-to-anterior gradient of striatal dopamine loss, yet the underlying upstream mechanisms remain unclear. We combined in vivo ¹⁸F-FPCIT dopamine transporter (DaT) PET/MRI, quantitative susceptibility mapping, and diffusion MRI tractography in 48 PD patients and 10 healthy controls to test whether substantia nigra pars compacta (SNc) iron and microstructural disruption mediate posterior putaminal vulnerability. PD patients showed marked posterior putamen (pPut) DaT reduction (~60%) and elevated SNc iron. SNc iron negatively correlated with striatal DaT availability, and nigrostriatal pathways to the pPut exhibited higher axial diffusivity. Serial mediation analyses demonstrated that SNc iron indirectly impaired striatal DaT function via reduced SNc DaT binding. Putaminal DaT-SBR robustly discriminated PD from controls (AUC 0.93–0.96), exceeding caudate performance. Transgenic and α-synuclein preformed fibril mouse models provided qualitative anatomical support. These findings identify SNc iron–related degeneration as a key driver of posterior striatal vulnerability in PD.",
  "abstract_shown": true,
  "affiliations": [
    "Department of Nuclear Medicine/PET Center, Huashan Hospital, Fudan University",
    "School of Medicine, Shanghai University",
    "Department of Neurology, Huashan Hospital, Fudan University",
    "United Imaging Healthcare Co., Ltd., Chengbei Road",
    "Institute for Biomedical Engineering, University, and ETH Zurich, Institute for Regenerative of Medicine, University of Zurich",
    "Department of Psychiatry and Psychotherapy, Marburg University",
    "Department of Neurology, Marburg University",
    "Department of Nuclear Medicine, Inselspital, University of Bern",
    "Beijing United Imaging Healthcare Co., Ltd.",
    "Institute of Biomedical Engineering, School of Life Sciences, Shanghai University"
  ],
  "article_type": null,
  "arxiv": null,
  "author_total": 26,
  "authors": [
    {
      "affs": [
        0
      ],
      "name": "Huamei Lin"
    },
    {
      "affs": [
        1
      ],
      "name": "Ying Zhang"
    },
    {
      "affs": [
        2
      ],
      "name": "Yixin Zhao"
    },
    {
      "affs": [
        3
      ],
      "name": "Yiman Wei"
    },
    {
      "affs": [
        4
      ],
      "name": "Benjamin F. Combes"
    },
    {
      "affs": [
        5
      ],
      "name": "Martin T. Henrich"
    },
    {
      "affs": [
        5
      ],
      "name": "Fanni F. Geibl"
    },
    {
      "affs": [
        6
      ],
      "name": "Wolfgang H. Oertel"
    },
    {
      "affs": [
        7
      ],
      "name": "Kuangyu Shi"
    },
    {
      "affs": [
        7
      ],
      "name": "Axel Rominger"
    },
    {
      "affs": [
        0
      ],
      "name": "Ping Wu"
    },
    {
      "affs": [
        0
      ],
      "name": "Jingjie Ge"
    },
    {
      "affs": [
        0
      ],
      "name": "Jing Wang"
    },
    {
      "affs": [
        0
      ],
      "name": "Jiaying Lu"
    },
    {
      "affs": [
        0
      ],
      "name": "Zizhao Ju"
    },
    {
      "affs": [
        0
      ],
      "name": "Qian Xu"
    },
    {
      "affs": [
        0
      ],
      "name": "Huiwei Zhang"
    },
    {
      "affs": [
        0
      ],
      "name": "Yunhao Yang"
    },
    {
      "affs": [
        3
      ],
      "name": "Zengping Lin"
    },
    {
      "affs": [
        8
      ],
      "name": "Yang Yang"
    },
    {
      "affs": [
        0
      ],
      "name": "Yihui Guan"
    },
    {
      "affs": [
        2
      ],
      "name": "Fengtao Liu"
    },
    {
      "affs": [
        2
      ],
      "name": "Jian Wang"
    },
    {
      "affs": [
        9
      ],
      "name": "Jiehui Jiang"
    },
    {
      "affs": [
        4
      ],
      "name": "Ruiqing Ni"
    },
    {
      "affs": [
        0
      ],
      "name": "Chuantao Zuo"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/fbb1q6p6b9p7m.bib",
  "cited_by": 0,
  "doi": "10.1038/s41531-026-01456-y",
  "fulltext_url": "https://doi.org/10.1038/s41531-026-01456-y",
  "id": "fbb1q6p6b9p7m",
  "issns": [
    "2373-8057"
  ],
  "landing_url": "https://doi.org/10.1038/s41531-026-01456-y",
  "language": "en",
  "licence": "CC-BY",
  "licence_label": "CC BY",
  "licence_source": "journal",
  "licence_url": "https://creativecommons.org/licenses/by/4.0/",
  "metadata_licence": null,
  "native_subjects": [
    [
      "lcc",
      "RC346-429"
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      "openalex",
      "2728|Parkinson's Disease Mechanisms and Treatments"
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  "pdf_url": "https://www.nature.com/articles/s41531-026-01456-y_reference.pdf",
  "pmcid": null,
  "pmid": null,
  "published": "2026-07-01",
  "publisher": "Nature Portfolio",
  "ris": "https://research.draconitic.com/paper/fbb1q6p6b9p7m.ris",
  "sources": [
    {
      "first_seen": "2026-10-30T13:45:42Z",
      "native_id": "2c8944fa6175451a976043a6b147c863",
      "source": "doaj",
      "url": "https://doi.org/10.1038/s41531-026-01456-y"
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  "subjects": [
    {
      "field": "medicine",
      "origin": "openalex:2728|Parkinson's Disease Mechanisms and Treatments",
      "subfield": "neurology"
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  ],
  "title": "Multimodal neuroimaging elucidates the posterior-to-anterior gradient of nigrostriatal degeneration in Parkinson’s disease",
  "title_text": "Multimodal neuroimaging elucidates the posterior-to-anterior gradient of nigrostriatal degeneration in Parkinson’s disease",
  "type": "peer-reviewed",
  "updated_at": "2026-10-30T13:45:42Z",
  "url": "https://research.draconitic.com/paper/fbb1q6p6b9p7m",
  "venue": "npj Parkinson's Disease",
  "versions": []
}