{
  "abstract": "Pathological tau disrupts neuronal activity and brain function in Alzheimer s disease and other tauopathies. However, the underlying mechanisms for neuronal network dysfunction remain largely unknown. Using human inducible pluripotent stem cell (iPSC) - derived neurons, we show that the familial MAPT P301L mutation leads to neuronal network hyperexcitability. Imbalanced excitation and inhibition were attributable to neuronal subtype-specific tau pathology that was associated with different alterations of tau interactomes in excitatory versus inhibitory neurons. Suppressing enhanced excitatory synaptic transmission or blocking Ca2+ influx resulting from enhanced P301L tau/AHNAK interaction in inhibitory neurons rescued the neuronal network hyperexcitability. This study expands our understanding on how disease-causing tau mutations alter the excitatory/inhibitory balance, leading to network dysfunction in human neurons.",
  "abstract_shown": true,
  "affiliations": [
    "New York University Grossman School of Medicine"
  ],
  "article_type": "New results",
  "arxiv": null,
  "author_total": 12,
  "authors": [
    {
      "affs": [
        0
      ],
      "name": "C. Ji"
    },
    {
      "name": "Y. Zhu"
    },
    {
      "name": "H. Erdjument-Bromage"
    },
    {
      "name": "S. C. Song"
    },
    {
      "name": "N. Chang"
    },
    {
      "name": "A. R. Liu"
    },
    {
      "name": "A. R. Lee"
    },
    {
      "name": "O. DeGulis"
    },
    {
      "name": "D. Schoppik"
    },
    {
      "name": "T. A. Neubert"
    },
    {
      "name": "H. D. Ryoo"
    },
    {
      "name": "E. Sigurdsson"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/ffh7jwj9xpea7.bib",
  "cited_by": 0,
  "doi": "10.64898/2026.10.05.756807",
  "fulltext_url": "https://www.biorxiv.org/content/10.64898/2026.10.05.756807v1.full",
  "id": "ffh7jwj9xpea7",
  "issns": [],
  "landing_url": "https://www.biorxiv.org/content/10.64898/2026.10.05.756807v1",
  "language": null,
  "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": [
    [
      "biorxiv",
      "neuroscience"
    ],
    [
      "openalex",
      "2737|Alzheimer's disease research and treatments"
    ]
  ],
  "openalex": "W7220693259",
  "pdf_url": "https://www.biorxiv.org/content/10.64898/2026.10.05.756807v1.full.pdf",
  "pmcid": null,
  "pmid": null,
  "published": "2026-10-05",
  "publisher": null,
  "ris": "https://research.draconitic.com/paper/ffh7jwj9xpea7.ris",
  "sources": [
    {
      "first_seen": "2026-10-30T12:26:16Z",
      "native_id": "10.64898/2026.10.05.756807",
      "source": "biorxiv",
      "url": "https://www.biorxiv.org/content/10.64898/2026.10.05.756807v1"
    }
  ],
  "subjects": [
    {
      "field": "biology",
      "origin": "biorxiv:neuroscience",
      "subfield": "neuroscience"
    }
  ],
  "title": "Pathological tau leads to network hyperexcitability through neuronal-subtype-specific functional impairment",
  "title_text": "Pathological tau leads to network hyperexcitability through neuronal-subtype-specific functional impairment",
  "type": "preprint",
  "updated_at": "2026-10-30T12:26:16Z",
  "url": "https://research.draconitic.com/paper/ffh7jwj9xpea7",
  "venue": "bioRxiv",
  "versions": []
}