{
  "abstract": "In familial Alzheimer's disease (FAD), mutations in the amyloid precursor protein gene (APP) accelerate the aggregation of Aβ peptide, leading to deposition of amyloid plaques within the brain. Conformational variants of Aβ aggregates (\"Aβ strains\") possess distinct pathological properties and may contribute to disease heterogeneity. While the Swedish APP mutation produces wild-type (WT) Aβ, the Arctic APP mutation generates E22G-mutant Aβ. To clarify whether different FAD mutations are sufficient to specify the formation of distinct Aβ strains, we performed Aβ seeding studies in AppNL-F knock-in mice. Aβ aggregates purified from Swedish and Arctic FAD human brains induced distinct neuropathological signatures, characterized by differences in the morphology and localization of the seeded Aβ deposits, which were preserved upon serial passage. Neither synthetic E22G-mutant Aβ aggregates nor Aβ aggregates isolated from the brains of transgenic mice producing E22G-mutant Aβ recapitulated the phenotype induced by Arctic FAD brain-derived Aβ aggregates upon injection into AppNL-F mice. Similarly, neither synthetic WT Aβ aggregates nor Aβ aggregates from Swedish APP-mutant transgenic mice reproduced the seeding behavior of Swedish FAD brain-derived Aβ aggregates. This suggests that it is the structure of Aβ aggregates rather than the Aβ sequence that dictates seeding activity. We conclude that de novo formation of FAD-relevant Aβ strains occurs exclusively in the human brain, implying the existence of human brain-specific cofactors that modulate Aβ aggregate structure and seeding activity.",
  "abstract_shown": true,
  "affiliations": [
    "Tanz Centre for Research in Neurodegenerative Diseases, University of Toronto, Krembil Discovery Tower, Rm. 4KD481, 60 Leonard Ave., Toronto, ON, M5T 0S8, Canada.",
    "Department of Biochemistry, University of Toronto, Toronto, ON, Canada.",
    "Department of Biochemistry and Molecular Biology, University of Santiago de Compostela, 15782, Santiago de Compostela, Spain.",
    "Krembil Brain Institute, University Health Network, Toronto, ON, Canada.",
    "Department of Public Health and Caring Sciences, Geriatrics, Uppsala University, Uppsala, Sweden.",
    "Department of Laboratory Medicine and Pathobiology, University of Toronto, Toronto, ON, Canada.",
    "Department of Physics, Chemistry, and Biology, Linköping University, Linköping, Sweden.",
    "Division for Neurogeriatrics, Centre for Alzheimer Research, Department of Neurobiology, Care Sciences and Society, Karolinska Institutet, Stockholm, Sweden.",
    "Unit for Hereditary Dementias, Karolinska University Hospital Solna, Stockholm, Sweden.",
    "Department of Medicine, University of Toronto, Toronto, ON, Canada.",
    "Tanz Centre for Research in Neurodegenerative Diseases, University of Toronto, Krembil Discovery Tower, Rm. 4KD481, 60 Leonard Ave., Toronto, ON, M5T 0S8, Canada. joel.watts@utoronto.ca.",
    "Department of Biochemistry, University of Toronto, Toronto, ON, Canada. joel.watts@utoronto.ca."
  ],
  "article_type": "research article",
  "arxiv": null,
  "author_total": 14,
  "authors": [
    {
      "affs": [
        0,
        1
      ],
      "name": "Alison Mao"
    },
    {
      "affs": [
        0,
        2
      ],
      "name": "Alejandro Ruiz-Riquelme"
    },
    {
      "affs": [
        0,
        1
      ],
      "name": "Marim M Barghash"
    },
    {
      "affs": [
        0,
        1
      ],
      "name": "Nicholas R G Silver"
    },
    {
      "affs": [
        0,
        1
      ],
      "name": "Heather H C Lau"
    },
    {
      "affs": [
        0
      ],
      "name": "Erica Stuart"
    },
    {
      "affs": [
        0,
        3
      ],
      "name": "Silvia Zampar"
    },
    {
      "affs": [
        4
      ],
      "name": "Dag Sehlin"
    },
    {
      "affs": [
        4
      ],
      "name": "Stina Syvänen"
    },
    {
      "affs": [
        0,
        5
      ],
      "name": "Michael S Pollanen"
    },
    {
      "affs": [
        6
      ],
      "name": "K Peter R Nilsson"
    },
    {
      "affs": [
        7,
        8
      ],
      "name": "Caroline Graff"
    },
    {
      "affs": [
        0,
        4,
        5,
        3,
        9
      ],
      "name": "Martin Ingelsson"
    },
    {
      "affs": [
        10,
        11
      ],
      "name": "Joel C Watts"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/a76m7gdn5c159.bib",
  "cited_by": 0,
  "doi": "10.1186/s40478-026-02390-z",
  "fulltext_url": "https://europepmc.org/articles/PMC13682113",
  "id": "a76m7gdn5c159",
  "issns": [
    "2051-5960"
  ],
  "landing_url": "https://europepmc.org/article/MED/42897618",
  "language": "eng",
  "licence": "CC-BY-NC-ND",
  "licence_label": "CC BY-NC-ND",
  "licence_source": "article",
  "licence_url": "https://creativecommons.org/licenses/by-nc-nd/4.0/",
  "metadata_licence": null,
  "native_subjects": [
    [
      "lcc",
      "RC346-429"
    ],
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      "openalex",
      "2737|Alzheimer's disease research and treatments"
    ]
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  "pdf_url": "https://europepmc.org/articles/PMC13682113?pdf=render",
  "pmcid": "PMC13682113",
  "pmid": "42897618",
  "published": "2026-07-01",
  "publisher": "BMC",
  "ris": "https://research.draconitic.com/paper/a76m7gdn5c159.ris",
  "sources": [
    {
      "first_seen": "2026-10-30T12:19:41Z",
      "native_id": "MED:42897618",
      "source": "europepmc",
      "url": "https://europepmc.org/article/MED/42897618"
    },
    {
      "first_seen": "2026-10-30T13:46:32Z",
      "native_id": "2c01a4ec436f4a2397d092bf7fa9fb14",
      "source": "doaj",
      "url": "https://doi.org/10.1186/s40478-026-02390-z"
    }
  ],
  "subjects": [
    {
      "field": "medicine",
      "origin": "openalex:2737|Alzheimer's disease research and treatments",
      "subfield": "physiology"
    }
  ],
  "title": "De novo formation of familial Alzheimer's disease-relevant Aβ strains occurs exclusively in the human brain.",
  "title_text": "De novo formation of familial Alzheimer's disease-relevant Aβ strains occurs exclusively in the human brain.",
  "type": "peer-reviewed",
  "updated_at": "2026-10-30T13:46:32Z",
  "url": "https://research.draconitic.com/paper/a76m7gdn5c159",
  "venue": "Acta neuropathologica communications",
  "versions": []
}