{
  "abstract": "Background\n\nAberrant reactivation of developmental cytoskeletal programs may contribute to Alzheimer's disease (AD). We tested whether a prespecified Arp2/3-RAC1-MYH10-KIF5C module is regulated by Erb-B2 receptor tyrosine kinase 4 (ERBB4) in an AD-model neuronal state, providing a perturbational test of the hypothesis that aberrant re-engagement of developmental cytoskeletal machinery contributes to AD.Methods\n\nWe performed a secondary analysis of publicly available single-nucleus RNA-sequencing data from ERBB4 perturbation experiments using pseudobulk analysis with the primary conservative excitatory-neuron classifier. A prespecified 10-gene module comprising Actr2, Actr3, Arpc1a, Arpc2, Arpc3, Arpc4, Arpc5, Rac1, Myh10, and Kif5c was tested using CAMERA and expression-matched permutation analyses.Results\n\nERBB4 disruption in 5 × FAD excitatory neurons downregulated all 10 module genes (CAMERA P = 0.0207). Arpc4, Arpc1a, and Kif5c remained significant after false-discovery-rate correction. Expression-matched permutation testing independently supported pathway downregulation (mean log-fold-change P = 0.0102; 10/10 genes down P = 0.0041; CAMERA permutation P = 0.0150). ERBB4 overexpression in wild-type neurons did not significantly alter the complete module, although Arpc5 was significantly induced, suggesting selective component responsiveness.Conclusions\n\nIndependent perturbational data support ERBB4-dependent regulation of a prespecified Arp2/3-centered cytoskeletal program in AD excitatory neurons, with effects dependent on the disease context.",
  "abstract_shown": true,
  "affiliations": [
    "Radiation Oncology, Icahn School of Medicine at Mount Sinai, New York, USA"
  ],
  "article_type": "research article",
  "arxiv": null,
  "author_total": 1,
  "authors": [
    {
      "affs": [
        0
      ],
      "name": "Steven Lehrer"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/9rznrdyp5d59d.bib",
  "cited_by": 0,
  "doi": "10.7759/cureus.117166",
  "fulltext_url": "https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13718877/?tool=EBI",
  "id": "9rznrdyp5d59d",
  "issns": [
    "2168-8184"
  ],
  "landing_url": "https://europepmc.org/article/PMC/PMC13718877",
  "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",
      "Genetics"
    ],
    [
      "heading",
      "Geriatrics"
    ],
    [
      "heading",
      "Neurology"
    ],
    [
      "openalex",
      "2737|Alzheimer's disease research and treatments"
    ]
  ],
  "openalex": "W7214706457",
  "pdf_url": "https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13718877/pdf/?tool=EBI",
  "pmcid": "PMC13718877",
  "pmid": "42960311",
  "published": "2026-09-29",
  "publisher": "Cureus Inc.",
  "ris": "https://research.draconitic.com/paper/9rznrdyp5d59d.ris",
  "sources": [
    {
      "first_seen": "2026-10-31T00:20:37Z",
      "native_id": "PMC:PMC13718877",
      "source": "europepmc",
      "url": "https://europepmc.org/article/PMC/PMC13718877"
    },
    {
      "first_seen": "2026-11-01T00:20:52Z",
      "native_id": "MED:42960311",
      "source": "europepmc",
      "url": "https://europepmc.org/article/MED/42960311"
    },
    {
      "first_seen": "2026-11-02T12:22:49Z",
      "native_id": "PMC13718877",
      "source": "pmc",
      "url": "https://doi.org/10.7759/cureus.117166"
    }
  ],
  "subjects": [
    {
      "field": "biology",
      "origin": "heading:Genetics",
      "subfield": "genetics-genomics"
    },
    {
      "field": "medicine",
      "origin": "heading:Neurology",
      "subfield": "neurology"
    }
  ],
  "title": "ERBB4 Perturbation Supports a Developmental Cytoskeletal Reactivation Hypothesis in Alzheimer’s Disease",
  "title_text": "ERBB4 Perturbation Supports a Developmental Cytoskeletal Reactivation Hypothesis in Alzheimer’s Disease",
  "type": "peer-reviewed",
  "updated_at": "2026-11-02T12:22:49Z",
  "url": "https://research.draconitic.com/paper/9rznrdyp5d59d",
  "venue": "Cureus",
  "versions": []
}