{
  "abstract": "How amyloid-{beta} (A{beta}) plaques and tau phosphorylation spatially relate to cell response and genetic variation in Alzheimer's disease (AD) brain is currently unclear. We established a pipeline to concurrently annotate A{beta} and AT8 ptau pathology and cell-specific MERFISH expression profiles in human control and AD hippocampus. We characterized expression signatures in glia and neurons proximal or distal to A{beta} plaques, AT8 ptau-enriched neurons, or A{beta} and AT8 ptau in combination, and used spatially-defined transcriptional signatures to infer pathology-associated states in large snRNA-seq datasets lacking spatial context. We characterized variants from 120 gene loci associated with AD risk that affect cell-specific gene expression within local pathological contexts. Astrocyte APOE4/E4 expression was specifically suppressed in proximity to A{beta} plaques, whereas other APOE genotypes were unaffected by A{beta} proximity. Together, this analysis pipeline couples expression profiles in proximity to A{beta} and tau pathology, and implicates AD cis-gene variants with spatial sensitivity to AD pathology.",
  "abstract_shown": true,
  "affiliations": [
    "Sanford Burnham Prebys Medical Discovery Institute"
  ],
  "article_type": "New results",
  "arxiv": null,
  "author_total": 8,
  "authors": [
    {
      "name": "C. H. Shi"
    },
    {
      "name": "B. Zhu"
    },
    {
      "name": "J. Pina-Crespo"
    },
    {
      "name": "W. N. Chen"
    },
    {
      "name": "G. V. Vo"
    },
    {
      "affs": [
        0
      ],
      "name": "H. Huang"
    },
    {
      "name": "K. Y. Yip"
    },
    {
      "affs": [
        0
      ],
      "name": "T. Y. Huang"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/e8975t4eq84aw.bib",
  "cited_by": 0,
  "doi": "10.64898/2026.10.15.759523",
  "fulltext_url": "https://www.biorxiv.org/content/10.64898/2026.10.15.759523v1.full",
  "id": "e8975t4eq84aw",
  "issns": [],
  "landing_url": "https://www.biorxiv.org/content/10.64898/2026.10.15.759523v1",
  "language": null,
  "licence": "CC-BY-NC",
  "licence_label": "CC BY-NC",
  "licence_source": "article",
  "licence_url": "https://creativecommons.org/licenses/by-nc/4.0/",
  "metadata_licence": null,
  "native_subjects": [
    [
      "biorxiv",
      "neuroscience"
    ],
    [
      "openalex",
      "2737|Alzheimer's disease research and treatments"
    ]
  ],
  "openalex": "W7223188008",
  "pdf_url": "https://www.biorxiv.org/content/10.64898/2026.10.15.759523v1.full.pdf",
  "pmcid": null,
  "pmid": null,
  "published": "2026-10-15",
  "publisher": null,
  "ris": "https://research.draconitic.com/paper/e8975t4eq84aw.ris",
  "sources": [
    {
      "first_seen": "2026-10-30T12:29:03Z",
      "native_id": "10.64898/2026.10.15.759523",
      "source": "biorxiv",
      "url": "https://www.biorxiv.org/content/10.64898/2026.10.15.759523v1"
    }
  ],
  "subjects": [
    {
      "field": "biology",
      "origin": "biorxiv:neuroscience",
      "subfield": "neuroscience"
    }
  ],
  "title": "Spatial proximity to AD pathology defines cell-type and genotype-specific characteristics in human AD hippocampus",
  "title_text": "Spatial proximity to AD pathology defines cell-type and genotype-specific characteristics in human AD hippocampus",
  "type": "preprint",
  "updated_at": "2026-10-30T12:29:03Z",
  "url": "https://research.draconitic.com/paper/e8975t4eq84aw",
  "venue": "bioRxiv",
  "versions": []
}