{
  "abstract": "Introduction\n\nApolipoprotein E ε4 (APOE ε4) carriership is associated with higher amyloid burden in Alzheimer's disease (AD), but whether it constrains the spatial predictability of amyloid deposition at the individual level remains unknown.Methods\n\nWe analyzed voxel-wise amyloid positron emission tomography data from 781 amyloid-positive individuals across two independent cohorts (Alzheimer's Disease Neuroimaging Initiative and Geneva Memory Center), spanning the full clinical continuum. Individual topographic similarity to canonical AD amyloid maps and within-group spatial homogeneity were assessed via voxel-wise correlations and linear regression adjusted for age, sex, and global amyloid burden.Results\n\nAPOE ε4 carriers exhibited amyloid distributions more aligned with canonical AD topographies than non-carriers (p < 0.001), with a clear gene-dose effect on within-group spatial homogeneity: Homozygotes showed the highest inter-subject consistency, followed by heterozygotes and non-carriers. Effects were robust across tracers, clinical stages, and cohorts.Discussion\n\nAPOE ε4 gene dose constrains the spatial predictability of amyloid accumulation, informing genotype-stratified approaches in anti-amyloid trials.",
  "abstract_shown": true,
  "affiliations": [
    "Laboratory of Neuroimaging of Aging (LANVIE), University of Geneva, Geneva, Switzerland.",
    "Geneva Memory Center, Department of Rehabilitation and Geriatrics, Geneva University Hospitals, Geneva, Switzerland.",
    "Laboratory of Neuroimaging and Innovative Molecular Tracers (NIMTlab), Geneva University Neurocenter and Faculty of Medicine, University of Geneva, Geneva, Switzerland.",
    "Laboratory of Alzheimer's Neuroimaging and Epidemiology (LANE), IRCCS Istituto Centro San Giovanni di Dio Fatebenefratelli, Brescia, Italy.",
    "Division of Nuclear Medicine and Molecular Imaging, Geneva University Hospitals, Geneva, Switzerland.",
    "CIBM Center for Biomedical Imaging, Geneva, Switzerland.",
    "Genoa section, National Institute of Nuclear Physics (INFN), Rome, Genoa, Italy."
  ],
  "article_type": "research article",
  "arxiv": null,
  "author_total": 9,
  "authors": [
    {
      "affs": [
        0,
        1
      ],
      "name": "Augusto J Mendes",
      "orcid": "0000-0002-9497-0707"
    },
    {
      "affs": [
        2
      ],
      "name": "Cecilia Boccalini"
    },
    {
      "affs": [
        0,
        1
      ],
      "name": "Federica Ribaldi"
    },
    {
      "affs": [
        3
      ],
      "name": "Michela Pievani"
    },
    {
      "affs": [
        2
      ],
      "name": "Débora Peretti"
    },
    {
      "affs": [
        2,
        4,
        5
      ],
      "name": "Valentina Garibotto"
    },
    {
      "affs": [
        6
      ],
      "name": "Andrea Chincarini"
    },
    {
      "affs": [
        0,
        1
      ],
      "name": "Giovanni B Frisoni"
    },
    {
      "name": "Alzheimer's Disease Neuroimaging Initiative"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/1qzvwp4kjfgqr.bib",
  "cited_by": 0,
  "doi": "10.1002/alz.71935",
  "fulltext_url": "https://europepmc.org/articles/PMC13719804",
  "id": "1qzvwp4kjfgqr",
  "issns": [
    "1552-5260",
    "1552-5279"
  ],
  "landing_url": "https://europepmc.org/article/MED/42957970",
  "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": [
    [
      "heading",
      "Research Article"
    ],
    [
      "openalex",
      "2738|Dementia and Cognitive Impairment Research"
    ]
  ],
  "openalex": "W7224735263",
  "pdf_url": "https://europepmc.org/articles/PMC13719804?pdf=render",
  "pmcid": "PMC13719804",
  "pmid": "42957970",
  "published": "2026-10-01",
  "publisher": "Wiley",
  "ris": "https://research.draconitic.com/paper/1qzvwp4kjfgqr.ris",
  "sources": [
    {
      "first_seen": "2026-11-01T00:20:44Z",
      "native_id": "MED:42957970",
      "source": "europepmc",
      "url": "https://europepmc.org/article/MED/42957970"
    },
    {
      "first_seen": "2026-11-02T12:23:42Z",
      "native_id": "PMC13719804",
      "source": "pmc",
      "url": "https://doi.org/10.1002/alz.71935"
    }
  ],
  "subjects": [
    {
      "field": "medicine",
      "origin": "openalex:2738|Dementia and Cognitive Impairment Research",
      "subfield": "psychiatry"
    }
  ],
  "title": "APOE ε4 gene dose drives a canonical and predictable topography of amyloid deposition.",
  "title_text": "APOE ε4 gene dose drives a canonical and predictable topography of amyloid deposition.",
  "type": "peer-reviewed",
  "updated_at": "2026-11-03T12:20:48Z",
  "url": "https://research.draconitic.com/paper/1qzvwp4kjfgqr",
  "venue": "Alzheimer's & dementia : the journal of the Alzheimer's Association",
  "versions": []
}