{
  "abstract": "Lipid droplets are dynamic cellular organelles that store neutral lipids and coordinate metabolic and stress-response pathways. In the brain, lipid droplets in glial cells, including astrocytes, have been implicated in Alzheimer's disease, but how genetic risk factors influence their composition and turnover remains poorly understood. APOE is the strongest genetic modulator of late-onset Alzheimer's disease and exists in common variants that confer decreased, neutral, or increased risk. Here we show that APOE genotype shapes the lipid droplet proteome, lipidome, and degradation dynamics in human induced pluripotent stem cell-derived astrocytes. By comparing oleic acid-treated astrocytes carrying APOE2, APOE3, or APOE4, we find that each variant is associated with distinct lipid droplet proteins and lipids. These molecular differences correspond to genotype-dependent changes in lipophagy, an autophagy-mediated pathway for lipid droplet clearance. Lipid droplets in APOE2 astrocytes undergo efficient autophagic turnover, whereas those in APOE4 astrocytes resist degradation. These findings identify impaired lipid droplet clearance as a potential mechanism linking APOE4 to Alzheimer's disease risk.",
  "abstract_shown": true,
  "affiliations": [
    "Genetics and Biochemistry Branch, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, MD, USA",
    "Center for Alzheimer's and Related Dementias (CARD), National Institute on Aging, National Institutes of Health, Bethesda, MD, USA",
    "Leiden University Medical Center, Center for Proteomics and Metabolomics, Leiden, the Netherlands",
    "Alzheimer Center Amsterdam, Department of Neurology, Amsterdam University Medical Center, Amsterdam Neuroscience, Amsterdam, the Netherlands",
    "Center for Neurogenomics and Cognitive Research, Vrije Universiteit Amsterdam, Amsterdam Neuroscience, Amsterdam, the Netherlands",
    "DataTecnica, Washington, DC, USA",
    "Laboratory of Molecular Biology, National Institute of Diabetes, Digestive and Kidney Diseases, National Institutes of Health, Bethesda, MD, USA",
    "Laboratory of Neurogenetics, National Institute on Aging, National Institutes of Health, Bethesda, MD, USA",
    "Center for Alzheimer's and Related Dementias (CARD), National Institute on Aging, National Institutes of Health, Bethesda, MD, USA. priyanka.narayan@nih.gov",
    "Genetics and Biochemistry Branch, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, MD, USA. priyanka.narayan@nih.gov"
  ],
  "article_type": null,
  "arxiv": null,
  "author_total": 17,
  "authors": [
    {
      "affs": [
        0
      ],
      "name": "Carla Cuní‐López",
      "orcid": "0000-0001-8804-8970"
    },
    {
      "affs": [
        0
      ],
      "name": "Jessica T. Root",
      "orcid": "0000-0002-9150-9579"
    },
    {
      "affs": [
        1
      ],
      "name": "Ying Hao",
      "orcid": "0000-0001-5053-4850"
    },
    {
      "affs": [
        2
      ],
      "name": "Niek Blomberg"
    },
    {
      "affs": [
        3,
        4
      ],
      "name": "Sascha Koppes-den Hertog",
      "orcid": "0000-0002-7372-8946"
    },
    {
      "affs": [
        1
      ],
      "name": "Dylan C. Sacks"
    },
    {
      "affs": [
        1,
        5
      ],
      "name": "Amber E. Trujillo",
      "orcid": "0000-0002-4541-4974"
    },
    {
      "affs": [
        6
      ],
      "name": "Rodolfo Ghirlando",
      "orcid": "0000-0003-4880-4959"
    },
    {
      "affs": [
        1
      ],
      "name": "Isabelle Kowal",
      "orcid": "0009-0004-4340-1418"
    },
    {
      "affs": [
        1
      ],
      "name": "Jacob Epstein",
      "orcid": "0009-0003-7979-3532"
    },
    {
      "affs": [
        0
      ],
      "name": "Linda G. Yang",
      "orcid": "0000-0002-1671-8792"
    },
    {
      "affs": [
        1,
        7
      ],
      "name": "Mark Cookson",
      "orcid": "0000-0002-1058-3831"
    },
    {
      "affs": [
        1
      ],
      "name": "Elise Marsan",
      "orcid": "0000-0003-1975-290X"
    },
    {
      "affs": [
        3,
        4
      ],
      "name": "Rik van der Kant",
      "orcid": "0000-0002-7023-0106"
    },
    {
      "affs": [
        2
      ],
      "name": "Martin A. Giera",
      "orcid": "0000-0003-1684-1894"
    },
    {
      "affs": [
        1
      ],
      "name": "Yue Andy Qi",
      "orcid": "0000-0003-1914-8710"
    },
    {
      "affs": [
        8,
        9
      ],
      "name": "Priyanka S. Narayan",
      "orcid": "0000-0002-9328-4959"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/781bbkz38qz2k.bib",
  "cited_by": 8,
  "doi": "10.1038/s41467-026-76565-6",
  "fulltext_url": null,
  "id": "781bbkz38qz2k",
  "issns": [
    "2041-1723"
  ],
  "landing_url": "https://doi.org/10.1038/s41467-026-76565-6",
  "language": "en",
  "licence": "CC-BY",
  "licence_label": "CC BY",
  "licence_source": "journal",
  "licence_url": "https://creativecommons.org/licenses/by/4.0/",
  "metadata_licence": null,
  "native_subjects": [
    [
      "openalex",
      "1303|Lipid metabolism and biosynthesis"
    ]
  ],
  "openalex": "W7203795734",
  "pdf_url": "https://www.nature.com/articles/s41467-026-76565-6_reference.pdf",
  "pmcid": "PMC12393358",
  "pmid": "40894647",
  "published": "2026-08-19",
  "publisher": "Nature Portfolio",
  "ris": "https://research.draconitic.com/paper/781bbkz38qz2k.ris",
  "sources": [
    {
      "first_seen": "2026-11-04T13:21:07Z",
      "native_id": "W7203795734",
      "source": "openalex",
      "url": "https://doi.org/10.1038/s41467-026-76565-6"
    }
  ],
  "subjects": [
    {
      "field": "biochemistry",
      "origin": "openalex:1303|Lipid metabolism and biosynthesis",
      "subfield": "enzymology-metabolism"
    }
  ],
  "title": "APOE genotypes differentially remodel the astrocytic lipid droplet proteome to shape lipid droplet dynamics",
  "title_text": "APOE genotypes differentially remodel the astrocytic lipid droplet proteome to shape lipid droplet dynamics",
  "type": "peer-reviewed",
  "updated_at": "2026-11-04T13:21:07Z",
  "url": "https://research.draconitic.com/paper/781bbkz38qz2k",
  "venue": "Nature Communications",
  "versions": []
}