{
  "abstract": "α-synuclein (αS), amyloid-β (Aβ), and Tau aggregates are hallmarks of many neurodegenerative diseases, yet the prevalence and nature of their nanoscopic co-assemblies remain poorly understood. Here, we adapt a single-molecule pull-down (SiMPull) assay to profile αS, Aβ, and Tau co-assemblies across post-mortem brain tissue homogenates, soluble brain fractions, human serum, cerebrospinal fluid, and saliva. We show that αS-Tau co-assemblies are abundant across all sample matrices, accounting for ~10-70% of total αS aggregates in both Parkinson's disease (PD) and control samples. Notably, αS-Tau co-assemblies in soluble brain fractions from controls exhibit higher Proteinase K (PK) resistance than those from PD cases. Biophysically, Tau accelerates αS aggregation in simple in vitro systems, but this effect is suppressed in complex environments. Together, this work establishes a framework for probing co-assemblies, revealing that αS-Tau species possess heterogeneous biophysical features and are unlikely to act as a single, uniformly toxic species in PD pathology.",
  "abstract_shown": true,
  "affiliations": [
    "Department of Chemistry, University of Cambridge, Cambridge, UK. yz566@cam.ac.uk.",
    "UK Dementia Research Institute at Cambridge, Cambridge, UK. yz566@cam.ac.uk.",
    "UK Dementia Research Institute at University College London, London, UK.",
    "Department of Chemistry, University of Cambridge, Cambridge, UK.",
    "UK Dementia Research Institute at Cambridge, Cambridge, UK.",
    "Department of Clinical Neurosciences, University of Cambridge, Cambridge, UK.",
    "Manchester Centre for Clinical Neurosciences, Salford Royal NHS Foundation Trust, Manchester Academic Health Science Centre, Manchester, UK.",
    "St. Thomas' Hospital London, London, UK.",
    "Department of Chemistry, University of Cambridge, Cambridge, UK. dk10012@cam.ac.uk.",
    "UK Dementia Research Institute at Cambridge, Cambridge, UK. dk10012@cam.ac.uk."
  ],
  "article_type": "research support, non u.s. gov't",
  "arxiv": null,
  "author_total": 16,
  "authors": [
    {
      "affs": [
        0,
        1
      ],
      "name": "Yu P Zhang"
    },
    {
      "affs": [
        2
      ],
      "name": "Amber Wallis"
    },
    {
      "affs": [
        2
      ],
      "name": "Clara Obensa Bertroli"
    },
    {
      "affs": [
        3,
        4
      ],
      "name": "Cherida Zhang"
    },
    {
      "affs": [
        3,
        4
      ],
      "name": "Melanie Burke"
    },
    {
      "affs": [
        3,
        4
      ],
      "name": "Florence Layburn"
    },
    {
      "affs": [
        3,
        4
      ],
      "name": "Evgeniia Lobanova",
      "orcid": "0000-0002-7605-5820"
    },
    {
      "affs": [
        3,
        5,
        6
      ],
      "name": "Martin Furlepa"
    },
    {
      "affs": [
        3,
        4
      ],
      "name": "Shekhar Kedia",
      "orcid": "0000-0002-9322-979X"
    },
    {
      "affs": [
        3,
        4
      ],
      "name": "Yuhao Cui",
      "orcid": "0009-0007-5761-8222"
    },
    {
      "affs": [
        3,
        4
      ],
      "name": "Prasanna Suresh",
      "orcid": "0009-0001-5298-5994"
    },
    {
      "affs": [
        3,
        4,
        7
      ],
      "name": "Woo Suk Yang"
    },
    {
      "affs": [
        5
      ],
      "name": "Annelies Quaegebeur"
    },
    {
      "affs": [
        2
      ],
      "name": "Tim Bartels",
      "orcid": "0000-0002-4071-5612"
    },
    {
      "affs": [
        5
      ],
      "name": "Caroline H Williams-Gray",
      "orcid": "0000-0002-2648-9743"
    },
    {
      "affs": [
        8,
        9
      ],
      "name": "David Klenerman",
      "orcid": "0000-0001-7116-6954"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/b8w9g58dp83b6.bib",
  "cited_by": 0,
  "doi": "10.1038/s41467-026-77728-1",
  "fulltext_url": "https://europepmc.org/articles/PMC13680374",
  "id": "b8w9g58dp83b6",
  "issns": [
    "2041-1723"
  ],
  "landing_url": "https://europepmc.org/article/MED/42897149",
  "language": "eng",
  "licence": "CC-BY",
  "licence_label": "CC BY",
  "licence_source": "article",
  "licence_url": "https://creativecommons.org/licenses/by/4.0/",
  "metadata_licence": null,
  "native_subjects": [
    [
      "openalex",
      "2728|Parkinson's Disease Mechanisms and Treatments"
    ]
  ],
  "openalex": "W7213550119",
  "pdf_url": "https://europepmc.org/articles/PMC13680374?pdf=render",
  "pmcid": "PMC13680374",
  "pmid": "42897149",
  "published": "2026-09-18",
  "publisher": null,
  "ris": "https://research.draconitic.com/paper/b8w9g58dp83b6.ris",
  "sources": [
    {
      "first_seen": "2026-10-30T12:19:41Z",
      "native_id": "MED:42897149",
      "source": "europepmc",
      "url": "https://europepmc.org/article/MED/42897149"
    }
  ],
  "subjects": [
    {
      "field": "medicine",
      "origin": "openalex:2728|Parkinson's Disease Mechanisms and Treatments",
      "subfield": "neurology"
    }
  ],
  "title": "Imaging nanoscopic co-assemblies of α-synuclein and Tau in human samples.",
  "title_text": "Imaging nanoscopic co-assemblies of α-synuclein and Tau in human samples.",
  "type": "peer-reviewed",
  "updated_at": "2026-10-30T12:19:41Z",
  "url": "https://research.draconitic.com/paper/b8w9g58dp83b6",
  "venue": "Nature communications",
  "versions": []
}