{
  "abstract": "Deficits in levels of phosphatidylinositol-4,5-bisphosphate [PI(4,5)P2] mediate Alzheimer’s disease (AD) pathogenesis and etiology. The depletion of PI(4,5)P2 has been reported in AD in both human brain and animal models. Repletion of the synaptic pool of PI(4,5)P2, through haploinsufficiency of the degrading enzyme, Synaptojanin 1, ameliorated behavioral deficits in a mouse model of AD, in spite of accumulating amyloid. In order to refine the contribution of PI(4,5)P2 to AD, we used optogenetic translocation of the PI(4,5)P2-synthesizing enzyme, phosphoinositide phosphate 4 kinase2A (PIP4K2A) to the plasma membrane using light inducible dimerizable cryptochrome 2 (CRY-2) and the transcription factor CRY2-binding domain (CIBN) fused to the plasma membrane-targeting motif (CAAX). Spatiotemporally controlled production of phosphatidylinositol-4,5-bisphosphate [PI(4,5)P2] at the plasma membrane induced amelioration of behavioral deficits in a mouse model of AD. Imaging mass spectrometry confirmed alteration of specific PI(4,5)P2 acyl species, di-oleate, indicating that precise PI(4,5)P2 species may ultimately be leveraged for therapeutic intervention.",
  "abstract_shown": true,
  "affiliations": [
    "Brain Health Imaging Institute, Department of Radiology, Weill Cornell Medicine, New York, NY USA",
    "Present Address: Department of Psychiatry, University of Pittsburgh, Pittsburgh, PA USA",
    "Columbia University Irving Medical Center, New York, NY USA",
    "Taub Institute for Research on Alzheimer’s Disease and the Aging Brain, New York, NY USA",
    "Department of Systems and Computational Biomedicine, Weill Cornell Medicine, New York, NY USA",
    "Englander Institute for Precision Medicine, Weill Cornell Medicine, New York, NY USA",
    "Department of Chemistry & Chemical Biology and Weill Institute for Cell and Molecular Biology, Cornell University, Ithaca, NY USA",
    "Present Address: Nathan Kline Institute, Orangeburg, NY USA"
  ],
  "article_type": "research article",
  "arxiv": null,
  "author_total": 13,
  "authors": [
    {
      "affs": [
        0,
        1
      ],
      "name": "Ana Paula Costa",
      "orcid": "0000-0003-0489-4315"
    },
    {
      "affs": [
        2,
        3
      ],
      "name": "Erica Acquarone",
      "orcid": "0000-0002-3266-8115"
    },
    {
      "affs": [
        0
      ],
      "name": "Artur Lazarian"
    },
    {
      "affs": [
        2
      ],
      "name": "Mathieu Herman"
    },
    {
      "affs": [
        0
      ],
      "name": "Krista M. Wartchow"
    },
    {
      "affs": [
        4
      ],
      "name": "Nicholas Bartelo",
      "orcid": "0000-0003-1815-0077"
    },
    {
      "affs": [
        0
      ],
      "name": "William J. Dartora",
      "orcid": "0000-0002-6164-0031"
    },
    {
      "affs": [
        4,
        5
      ],
      "name": "Jan Krumsiek",
      "orcid": "0000-0003-4734-3791"
    },
    {
      "affs": [
        6
      ],
      "name": "Xiang-Ling Li"
    },
    {
      "affs": [
        6
      ],
      "name": "Jeremy M. Baskin",
      "orcid": "0000-0003-2939-3138"
    },
    {
      "affs": [
        2,
        3
      ],
      "name": "Ottavio Arancio",
      "orcid": "0000-0001-6335-164X"
    },
    {
      "affs": [
        2,
        3,
        7
      ],
      "name": "S. Abid Hussaini"
    },
    {
      "affs": [
        0,
        2,
        3
      ],
      "name": "Laura Beth McIntire",
      "orcid": "0000-0002-9565-8889"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/6zph30fd9fxm3.bib",
  "cited_by": 0,
  "doi": "10.1038/s42003-026-10517-0",
  "fulltext_url": "https://pmc.ncbi.nlm.nih.gov/articles/PMC13740230/",
  "id": "6zph30fd9fxm3",
  "issns": [
    "2399-3642"
  ],
  "landing_url": "https://doi.org/10.1038/s42003-026-10517-0",
  "language": "en",
  "licence": "CC-BY-NC-ND-4.0",
  "licence_label": "CC BY-NC-ND 4.0",
  "licence_source": "article",
  "licence_url": "https://creativecommons.org/licenses/by-nc-nd/4.0/",
  "metadata_licence": null,
  "native_subjects": [
    [
      "heading",
      "Article"
    ],
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      "openalex",
      "2804|Alzheimer's disease research and treatments"
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  "pdf_url": "https://www.nature.com/articles/s42003-026-10517-0_reference.pdf",
  "pmcid": "PMC13740230",
  "pmid": "42448968",
  "published": "2026-07-14",
  "publisher": "Nature Publishing Group",
  "ris": "https://research.draconitic.com/paper/6zph30fd9fxm3.ris",
  "sources": [
    {
      "first_seen": "2026-11-10T12:21:31Z",
      "native_id": "PMC13740230",
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      "url": "https://doi.org/10.1038/s42003-026-10517-0"
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  "subjects": [
    {
      "field": "biology",
      "origin": "openalex:2804|Alzheimer's disease research and treatments",
      "subfield": "neuroscience"
    }
  ],
  "title": "Temporal and spatial control of phosphatidylinositides using optogenetics ameliorates behavioral deficits in an Alzheimer’s disease mouse model",
  "title_text": "Temporal and spatial control of phosphatidylinositides using optogenetics ameliorates behavioral deficits in an Alzheimer’s disease mouse model",
  "type": "peer-reviewed",
  "updated_at": "2026-11-10T12:21:31Z",
  "url": "https://research.draconitic.com/paper/6zph30fd9fxm3",
  "venue": "Communications Biology",
  "versions": []
}