{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,19]],"date-time":"2026-03-19T14:44:40Z","timestamp":1773931480199,"version":"3.50.1"},"reference-count":115,"publisher":"MDPI AG","issue":"6","license":[{"start":{"date-parts":[[2026,3,19]],"date-time":"2026-03-19T00:00:00Z","timestamp":1773878400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Program for Neuropsychiatric Research, McLean Hospital"},{"DOI":"10.13039\/100000057","name":"NIGMS","doi-asserted-by":"publisher","award":["R35GM134949"],"award-info":[{"award-number":["R35GM134949"]}],"id":[{"id":"10.13039\/100000057","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cells"],"abstract":"<jats:p>Lipid abnormalities have been observed in brain, cerebrospinal fluid (CSF), and blood in association with late-onset Alzheimer\u2019s disease (LOAD). It is unknown which of these abnormalities are precursors to LOAD and which are concomitants of illness or its treatment. Inherent abnormalities can be identified in induced pluripotent stem cell (iPSC)-derived brain cells. These cells lack markers associated with aging and environmental exposures. The iPSC lines of patients with LOAD or healthy individuals were differentiated to astrocytes. Astrocytes are crucial to neural activity and health, and altered astrocyte functions are associated with LOAD pathology. Lipidomics analyses were performed on whole-cell and mitochondria-enriched fractions. Large reductions in cholesterol esters (CEs) and imbalances in fatty acids (FAs) were observed in LOAD-associated cells or their mitochondria. There were only modest differences in other lipid classes, including membrane structural lipids. The findings identify abnormalities in CEs, as well as in FAs, as inherent abnormalities and likely precursors to LOAD. These differences implicate mechanisms contributing to disease pathogenesis. Further study may lead to early interventions to prevent or delay LOAD.<\/jats:p>","DOI":"10.3390\/cells15060549","type":"journal-article","created":{"date-parts":[[2026,3,19]],"date-time":"2026-03-19T11:50:36Z","timestamp":1773921036000},"page":"549","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Inherent Lipid Composition Abnormalities in Astrocytes Associated with Late-Onset Alzheimer\u2019s Disease (LOAD)"],"prefix":"10.3390","volume":"15","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-8861-6285","authenticated-orcid":false,"given":"Bruce M.","family":"Cohen","sequence":"first","affiliation":[{"name":"Program for Neuropsychiatric Research, McLean Hospital, 115 Mill St., Belmont, MA 02478, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7045-0603","authenticated-orcid":false,"given":"Eunjung","family":"Koh","sequence":"additional","affiliation":[{"name":"Program for Neuropsychiatric Research, McLean Hospital, 115 Mill St., Belmont, MA 02478, USA"},{"name":"Laboratory for Translational Research on Neurodegeneration, McLean Hospital, 115 Mill St., Belmont, MA 02478, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2234-3683","authenticated-orcid":false,"given":"Kandice R.","family":"Levental","sequence":"additional","affiliation":[{"name":"Department of Molecular Physiology and Biological Physics, University of Virginia School of Medicine, 200 Jeanette Lancaster Way, Charlottesville, VA 22903, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1206-9545","authenticated-orcid":false,"given":"Ilya","family":"Levental","sequence":"additional","affiliation":[{"name":"Department of Molecular Physiology and Biological Physics, University of Virginia School of Medicine, 200 Jeanette Lancaster Way, Charlottesville, VA 22903, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7979-8171","authenticated-orcid":false,"given":"Kai-Christian","family":"Sonntag","sequence":"additional","affiliation":[{"name":"Program for Neuropsychiatric Research, McLean Hospital, 115 Mill St., Belmont, MA 02478, USA"},{"name":"Laboratory for Translational Research on Neurodegeneration, McLean Hospital, 115 Mill St., Belmont, MA 02478, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2026,3,19]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","unstructured":"(2024). 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