The protein and lipid compositions of brain apolipoprotein E particles are cell type-specific
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Le résumé fourni par la source
Abstract Genetic variation in APOE , which encodes a lipid transporter apolipoprotein E (apoE), is the strongest risk factor for late-onset Alzheimer’s disease (AD). Although central nervous system (CNS) apoE is produced by various cell types, including astrocytes, microglia, and pericytes, it is unclear whether apoE lipoproteins are a homogeneous population or if their molecular composition varies depending on their cellular origin. Emerging evidence suggests that CNS apoE lipoproteins contribute to AD-related processes, including amyloid deposition, neuroinflammation, synaptic maintenance, and blood–brain barrier function in a cell type-specific manner. We hypothesized that the compositions of CNS apoE lipoproteins depend on their cellular origin and investigated the lipid and protein profiles of apoE particles secreted by induced pluripotent stem cell (iPSC)-derived brain cells and derived from human cerebrospinal fluid (CSF) using liquid chromatography-mass spectrometry (LC-MS/MS). Our results demonstrate that astrocytes, pericytes, and microglia secrete apoE lipoproteins with distinct, cell type-specific lipid and protein profiles. Astrocyte-secreted particles were enriched in sphingomyelins and proteins linked to lipid metabolism, whereas pericyte-secreted particles contained ether-linked phospholipids and proteins associated with antioxidant activity. The lipidation of microglial apoE was markedly lower, but these particles had higher levels of transferrin, apoC-II, and cathepsin D. Notably, one-third of identified features were cell type-specific, highlighting the substantial molecular specialization across cell types. Most lipids and proteins identified in cell-secreted apoE were also detected in CSF-derived particles. Our findings advance the understanding of apoE biology by shifting the focus from apoE as a single, homogeneous entity to a diverse population of complex particles, the composition of which might be linked to functions in health and neurodegenerative diseases.
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Le contrôle bibliographique ouvert
DOI retrouvé dans Crossref DOI retrouvé ; titre concordant.
- Titre Crossref
- The protein and lipid compositions of brain apolipoprotein E particles are cell type-specific
- Date Crossref
- 14/09/2026
- Éditeur
- openRxiv
- Type
- posted-content
Ce recoupement confirme des métadonnées liées au DOI. Il ne confirme ni la méthode ni les conclusions de l’étude, et il ne compte pas comme une seconde source scientifique indépendante.
Où se fait cette recherche
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University of Zurich Life Science Zurich Graduate School pays non établi dans la noticeUniversité ou école supérieure
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University Hospital Zurich pays non établi dans la noticeÉtablissement de santé
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Life Science Zurich pays non établi dans la noticeUniversité ou école supérieure
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SIB Swiss Institute of Bioinformatics pays non établi dans la noticeOrganisation à but non lucratif
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ETH Zurich pays non établi dans la noticeUniversité ou école supérieure
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Institute for Biomedical Engineering pays non établi dans la noticeStructure de recherche
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Functional Genomics Center Zurich pays non établi dans la noticeStructure de recherche
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University Hospital of Zurich Institute of Clinical Chemistry pays non établi dans la noticeUniversité ou école supérieure
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Institute of Molecular and Translational Medicine pays non établi dans la noticeStructure de recherche
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Swiss Multi-Omics Center pays non établi dans la noticeInstitution
Life Science Zurich Graduate School — University of Zurich, University Hospital Zurich et Life Science Zurich, avec 7 autres affiliations.
Une affiliation ne permet pas de déduire la nationalité d’un auteur.