{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"institution":[{"name":"bioRxiv"}],"indexed":{"date-parts":[[2026,10,7]],"date-time":"2026-10-07T01:57:46Z","timestamp":1791338266222,"version":"4.3.1"},"posted":{"date-parts":[[2024,7,3]]},"group-title":"Neuroscience","reference-count":94,"publisher":"openRxiv","license":[{"start":{"date-parts":[[2024,7,3]],"date-time":"2024-07-03T00:00:00Z","timestamp":1719964800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"accepted":{"date-parts":[[2024,7,3]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                <jats:p>\n                  Lipid changes in the brain have been implicated in many neurodegenerative diseases including Alzheimer\u2019s Disease (AD), Parkinson\u2019s disease and Amyotrophic Lateral Sclerosis. To facilitate comparative lipidomic research across brain-diseases we established a data commons named the Neurolipid Atlas, that we have pre-populated with novel human, mouse and isogenic induced pluripotent stem cell (iPSC)-derived lipidomics data for different brain diseases. We show that iPSC-derived neurons, microglia and astrocytes display distinct lipid profiles that recapitulate\n                  <jats:italic>in vivo<\/jats:italic>\n                  lipotypes. Leveraging multiple datasets, we show that the AD risk gene ApoE4 drives cholesterol ester (CE) accumulation in human astrocytes recapitulating CE accumulation measured in the human AD brain. Multi-omic interrogation of iPSC-derived astrocytes revealed that cholesterol plays a major role in astrocyte interferon-dependent pathways such as the immunoproteasome and major histocompatibility complex (MHC) class I antigen presentation. We show that through enhanced cholesterol esterification ApoE4 suppresses immune activation of astrocytes. Our novel data commons, available at neurolipidatlas.com, provides a user-friendly tool and knowledge base for a better understanding of lipid dyshomeostasis in neurodegenerative diseases.\n                <\/jats:p>","DOI":"10.1101\/2024.07.01.601474","type":"posted-content","created":{"date-parts":[[2024,7,3]],"date-time":"2024-07-03T15:40:16Z","timestamp":1720021216000},"source":"Crossref","is-referenced-by-count":23,"title":["The Neurolipid Atlas: a lipidomics resource for neurodegenerative diseases uncovers cholesterol as a regulator of astrocyte reactivity impaired by ApoE4"],"prefix":"10.64898","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-6003-4048","authenticated-orcid":false,"given":"Femke M.","family":"Feringa","sequence":"first","affiliation":[{"name":"Center for Neurogenomics and Cognitive Research, Vrije Universiteit Amsterdam, Amsterdam Neuroscience, Amsterdam, the Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sascha J.","family":"Koppes-den Hertog","sequence":"additional","affiliation":[{"name":"Center for Neurogenomics and Cognitive Research, Vrije Universiteit Amsterdam, Amsterdam Neuroscience, Amsterdam, the Netherlands"},{"name":"Alzheimer Center Amsterdam, Department of Neurology, Amsterdam University Medical Center, Amsterdam Neuroscience, Amsterdam, the Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lian","family":"Wang","sequence":"additional","affiliation":[{"name":"Leiden University Medical Center, Center for Proteomics and Metabolomics, Leiden, the Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rico J.E.","family":"Derks","sequence":"additional","affiliation":[{"name":"Leiden University Medical Center, Center for Proteomics and Metabolomics, Leiden, the Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Iris","family":"Kruijff","sequence":"additional","affiliation":[{"name":"Center for Neurogenomics 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Amsterdam Neuroscience, Amsterdam, the Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ricardo","family":"Miramontes","sequence":"additional","affiliation":[{"name":"Department of Psychiatry and Human Behavior, University of California, Irvine, CA, USA"},{"name":"Department of Neurobiology and Behavior, University of California, Irvine, CA, USA"},{"name":"Institute for Memory Impairments and Neurological Disorders, University of California, Irvine, CA, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nadine","family":"P\u00f6mpner","sequence":"additional","affiliation":[{"name":"Leibniz Institute on Aging, Fritz Lipmann Institute, Jena, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Niek","family":"Blomberg","sequence":"additional","affiliation":[{"name":"Leiden University Medical Center, Center for Proteomics and Metabolomics, Leiden, the 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