{
  "abstract": "Alzheimer’s disease, the most common age-related neurodegenerative disease, is closely associated with both amyloid-ß plaque and neuroinflammation. Two thirds of Alzheimer’s disease patients are females and they have a higher disease risk. Moreover, women with Alzheimer’s disease have more extensive brain histological changes than men along with more severe cognitive symptoms and neurodegeneration. To identify how sex difference induces structural brain changes, we performed unbiased massively parallel single nucleus RNA sequencing on Alzheimer’s disease and control brains focusing on the middle temporal gyrus, a brain region strongly affected by the disease but not previously studied with these methods. We identified a subpopulation of selectively vulnerable layer 2/3 excitatory neurons that that were RORB-negative and CDH9-expressing. This vulnerability differs from that reported for other brain regions, but there was no detectable difference between male and female patterns in middle temporal gyrus samples. Disease-associated, but sex-independent, reactive astrocyte signatures were also present. In clear contrast, the microglia signatures of diseased brains differed between males and females. Combining single cell transcriptomic data with results from genome-wide association studies (GWAS), we identified MERTK genetic variation as a risk factor for Alzheimer’s disease selectively in females. Taken together, our single cell dataset revealed a unique cellular-level view of sex-specific transcriptional changes in Alzheimer’s disease, illuminating GWAS identification of sex-specific Alzheimer’s risk genes. These data serve as a rich resource for interrogation of the molecular and cellular basis of Alzheimer’s disease.",
  "abstract_shown": true,
  "affiliations": [
    "Department of Neurology, Yale University School of Medicine, New Haven, CT, USA",
    "Department of Neuroscience, Yale University School of Medicine, New Haven, CT, USA",
    "Department of Biostatistics, Yale University School of Public Health, New Haven, CT, USA",
    "Yale University",
    "Department of Molecular, Cellular, and Developmental Biology, Yale University, New Haven, CT, USA",
    "Cellular Neuroscience, Neurodegeneration and Repair Program, Yale University School of Medicine, New Haven, CT, USA",
    "Department of Immunobiology, Yale University School of Medicine, New Haven, CT, USA",
    "Department of Pharmacology, Yale University School of Medicine, New Haven, CT, USA",
    "University of Miami",
    "Department of Pathology, Yale University School of Medicine, New Haven, CT, USA"
  ],
  "article_type": null,
  "arxiv": null,
  "author_total": 23,
  "authors": [
    {
      "affs": [
        0,
        1
      ],
      "name": "Le Zhang",
      "orcid": "0000-0002-4860-831X"
    },
    {
      "affs": [
        2,
        3,
        0
      ],
      "name": "Tianyu Liu",
      "orcid": "0000-0002-9412-6573"
    },
    {
      "affs": [
        0
      ],
      "name": "Chuan H. He"
    },
    {
      "affs": [
        0,
        4
      ],
      "name": "Anthony Russo"
    },
    {
      "affs": [
        0,
        1
      ],
      "name": "Sarah Coffey",
      "orcid": "0000-0003-3631-2228"
    },
    {
      "affs": [
        0,
        2
      ],
      "name": "Dominic Yin",
      "orcid": "0000-0001-7733-9326"
    },
    {
      "affs": [
        1,
        2
      ],
      "name": "I-Uen Yvonne Hsu",
      "orcid": "0000-0002-4089-6601"
    },
    {
      "affs": [
        2
      ],
      "name": "Chi Zhang",
      "orcid": "0000-0002-2682-4142"
    },
    {
      "affs": [
        2,
        5,
        0,
        1
      ],
      "name": "Yixuan Ye",
      "orcid": "0000-0002-2643-665X"
    },
    {
      "affs": [
        2,
        5,
        0,
        1
      ],
      "name": "Chang Su",
      "orcid": "0000-0002-8704-1512"
    },
    {
      "affs": [
        5,
        0,
        1,
        6,
        7
      ],
      "name": "Joshua M. Spurrier",
      "orcid": "0000-0002-6267-7231"
    },
    {
      "affs": [
        5,
        0,
        1,
        7
      ],
      "name": "LaShae Nicholson",
      "orcid": "0000-0002-5171-181X"
    },
    {
      "affs": [
        8,
        5,
        9
      ],
      "name": "Brian W. Kunkle",
      "orcid": "0000-0002-9515-5157"
    },
    {
      "affs": [
        8,
        6,
        0
      ],
      "name": "Eden R. Martin",
      "orcid": "0000-0002-4035-9152"
    },
    {
      "affs": [
        8,
        2
      ],
      "name": "Omar G. Rodriguez"
    },
    {
      "affs": [
        8,
        5,
        0,
        1
      ],
      "name": "Lissette Gomez"
    },
    {
      "affs": [
        1
      ],
      "name": "Rui B. Chang",
      "orcid": "0000-0001-6953-2943"
    },
    {
      "affs": [
        6,
        7
      ],
      "name": "Carla Vanina Rothlin",
      "orcid": "0000-0002-5693-5572"
    },
    {
      "affs": [
        0,
        7
      ],
      "name": "Sourav Ghosh",
      "orcid": "0000-0001-5990-8708"
    },
    {
      "affs": [
        5,
        9
      ],
      "name": "Pallavi P. Gopal",
      "orcid": "0000-0003-4708-8479"
    },
    {
      "affs": [
        6,
        0
      ],
      "name": "David A. Hafler",
      "orcid": "0000-0003-4664-535X"
    },
    {
      "affs": [
        2
      ],
      "name": "Hongyu Zhao",
      "orcid": "0000-0003-1195-9607"
    },
    {
      "affs": [
        5,
        0,
        1
      ],
      "name": "Stephen M. Strittmatter",
      "orcid": "0000-0001-8188-3092"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/9bhg44scvwt3n.bib",
  "cited_by": 22,
  "doi": "10.1177/13872877261480719",
  "fulltext_url": null,
  "id": "9bhg44scvwt3n",
  "issns": [
    "1387-2877",
    "1875-8908"
  ],
  "landing_url": "https://doi.org/10.1177/13872877261480719",
  "language": "en",
  "licence": "CC-BY-NC",
  "licence_label": "CC BY-NC",
  "licence_source": "journal",
  "licence_url": "https://creativecommons.org/licenses/by-nc/4.0/",
  "metadata_licence": null,
  "native_subjects": [
    [
      "openalex",
      "2737|Alzheimer's disease research and treatments"
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      "2804|Alzheimer's disease research and treatments"
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  "openalex": "W4321605297",
  "pdf_url": null,
  "pmcid": "PMC9980267",
  "pmid": "36865305",
  "published": "2026-09-01",
  "publisher": "IOS Press",
  "ris": "https://research.draconitic.com/paper/9bhg44scvwt3n.ris",
  "sources": [
    {
      "first_seen": "2026-10-30T13:26:54Z",
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      "url": "https://doi.org/10.1177/13872877261480719"
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  "subjects": [
    {
      "field": "biology",
      "origin": "openalex:2804|Alzheimer's disease research and treatments",
      "subfield": "neuroscience"
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    {
      "field": "medicine",
      "origin": "openalex:2737|Alzheimer's disease research and treatments",
      "subfield": "physiology"
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  ],
  "title": "Single-cell transcriptomic atlas of Alzheimer's disease middle temporal gyrus reveals region, cell type, and sex specificity of gene expression with novel genetic risk for MERTK in female",
  "title_text": "Single-cell transcriptomic atlas of Alzheimer's disease middle temporal gyrus reveals region, cell type, and sex specificity of gene expression with novel genetic risk for MERTK in female",
  "type": "peer-reviewed",
  "updated_at": "2026-11-08T13:20:48Z",
  "url": "https://research.draconitic.com/paper/9bhg44scvwt3n",
  "venue": "Journal of Alzheimer s Disease",
  "versions": []
}