{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,27]],"date-time":"2026-10-27T15:50:12Z","timestamp":1793116212800,"version":"4.5.0"},"reference-count":111,"publisher":"Elsevier BV","license":[{"start":{"date-parts":[[2025,9,1]],"date-time":"2025-09-01T00:00:00Z","timestamp":1756684800000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/tdm\/userlicense\/1.0\/"},{"start":{"date-parts":[[2025,9,1]],"date-time":"2025-09-01T00:00:00Z","timestamp":1756684800000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/legal\/tdmrep-license"},{"start":{"date-parts":[[2025,9,1]],"date-time":"2025-09-01T00:00:00Z","timestamp":1756684800000},"content-version":"stm-asf","delay-in-days":0,"URL":"https:\/\/doi.org\/10.15223\/policy-017"},{"start":{"date-parts":[[2025,9,1]],"date-time":"2025-09-01T00:00:00Z","timestamp":1756684800000},"content-version":"stm-asf","delay-in-days":0,"URL":"https:\/\/doi.org\/10.15223\/policy-037"},{"start":{"date-parts":[[2025,9,1]],"date-time":"2025-09-01T00:00:00Z","timestamp":1756684800000},"content-version":"stm-asf","delay-in-days":0,"URL":"https:\/\/doi.org\/10.15223\/policy-012"},{"start":{"date-parts":[[2025,9,1]],"date-time":"2025-09-01T00:00:00Z","timestamp":1756684800000},"content-version":"stm-asf","delay-in-days":0,"URL":"https:\/\/doi.org\/10.15223\/policy-029"},{"start":{"date-parts":[[2025,9,1]],"date-time":"2025-09-01T00:00:00Z","timestamp":1756684800000},"content-version":"stm-asf","delay-in-days":0,"URL":"https:\/\/doi.org\/10.15223\/policy-004"}],"funder":[{"DOI":"10.13039\/501100004478","name":"Beijing Union University","doi-asserted-by":"publisher","award":["ZKZD202304"],"award-info":[{"award-number":["ZKZD202304"]}],"id":[{"id":"10.13039\/501100004478","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100004478","name":"Beijing Union University","doi-asserted-by":"publisher","award":["ZK70202101"],"award-info":[{"award-number":["ZK70202101"]}],"id":[{"id":"10.13039\/501100004478","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["elsevier.com","sciencedirect.com"],"crossmark-restriction":true},"short-container-title":["Biochemical and Biophysical Research Communications"],"published-print":{"date-parts":[[2025,9]]},"DOI":"10.1016\/j.bbrc.2025.152335","type":"journal-article","created":{"date-parts":[[2025,7,15]],"date-time":"2025-07-15T07:55:30Z","timestamp":1752566130000},"page":"152335","update-policy":"https:\/\/doi.org\/10.1016\/elsevier_cm_policy","source":"Crossref","is-referenced-by-count":19,"special_numbering":"C","title":["APOE4-driven lipid metabolic dysregulation in Alzheimer's disease: Multi-pathway mechanisms and therapeutic perspectives"],"prefix":"10.1016","volume":"778","author":[{"given":"Wen-Xuan","family":"Zhang","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yi-Liang","family":"Yang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jia-Xin","family":"Yu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Li-Hong","family":"Jia","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3574-5286","authenticated-orcid":false,"given":"Han-Chang","family":"Huang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"78","reference":[{"issue":"3","key":"10.1016\/j.bbrc.2025.152335_bib1","doi-asserted-by":"crossref","first-page":"1047","DOI":"10.1152\/physrev.00015.2020","article-title":"The complexity of Alzheimer's disease: an evolving puzzle","volume":"101","author":"Ferrari","year":"2021","journal-title":"Physiol. Rev."},{"issue":"1","key":"10.1016\/j.bbrc.2025.152335_bib2","doi-asserted-by":"crossref","first-page":"68","DOI":"10.1016\/S1474-4422(20)30412-9","article-title":"APOE and Alzheimer's disease: advances in genetics, pathophysiology, and therapeutic approaches","volume":"20","author":"Serrano-Pozo","year":"2021","journal-title":"Lancet Neurol."},{"issue":"10440","key":"10.1016\/j.bbrc.2025.152335_bib3","doi-asserted-by":"crossref","first-page":"2133","DOI":"10.1016\/S0140-6736(24)00757-8","volume":"403","year":"2024","journal-title":"Lancet (London, England)"},{"issue":"2","key":"10.1016\/j.bbrc.2025.152335_bib4","doi-asserted-by":"crossref","first-page":"459","DOI":"10.3233\/JAD-180740","article-title":"The role of apolipoprotein E isoforms in Alzheimer's disease","volume":"68","author":"Roda","year":"2019","journal-title":"J. Alzheim. Dis.: JAD"},{"issue":"9","key":"10.1016\/j.bbrc.2025.152335_bib5","article-title":"Apolipoprotein E and Alzheimer disease: pathobiology and targeting strategies","volume":"15","author":"Y","year":"2019","journal-title":"Nat. Rev. Neurol."},{"issue":"5","key":"10.1016\/j.bbrc.2025.152335_bib6","doi-asserted-by":"crossref","first-page":"1284","DOI":"10.1038\/s41591-024-02931-w","article-title":"APOE4 homozygozity represents a distinct genetic form of Alzheimer's disease","volume":"30","author":"Fortea","year":"2024","journal-title":"Nat. Med."},{"issue":"6512","key":"10.1016\/j.bbrc.2025.152335_bib7","doi-asserted-by":"crossref","first-page":"61","DOI":"10.1126\/science.abb8575","article-title":"Translating genetic risk of Alzheimer's disease into mechanistic insight and drug targets","volume":"370","author":"Sierksma","year":"2020","journal-title":"Science (New York, N.Y.)"},{"issue":"4","key":"10.1016\/j.bbrc.2025.152335_bib8","doi-asserted-by":"crossref","first-page":"347","DOI":"10.1016\/j.biopsych.2017.03.003","article-title":"Apolipoprotein E, receptors, and modulation of Alzheimer's disease","volume":"83","author":"Zhao","year":"2018","journal-title":"Biol. Psychiatry"},{"issue":"1","key":"10.1016\/j.bbrc.2025.152335_bib9","first-page":"11","article-title":"Human apolipoprotein E isoprotein subclasses are genetically determined","volume":"33","author":"Zannis","year":"1981","journal-title":"Am. J. Hum. Genet."},{"issue":"2","key":"10.1016\/j.bbrc.2025.152335_bib10","doi-asserted-by":"crossref","first-page":"860","DOI":"10.1016\/S0021-9258(17)43536-8","article-title":"Defective hepatic lipoprotein receptor binding of beta-very low density lipoproteins from type III hyperlipoproteinemic patients. Importance of apolipoprotein E","volume":"259","author":"Hui","year":"1984","journal-title":"J. Biol. Chem."},{"issue":"1","key":"10.1016\/j.bbrc.2025.152335_bib11","doi-asserted-by":"crossref","first-page":"62","DOI":"10.1186\/s13024-022-00566-4","article-title":"APOE in the bullseye of neurodegenerative diseases: impact of the APOE genotype in Alzheimer's disease pathology and brain diseases","volume":"17","author":"Fern\u00e1ndez-Calle","year":"2022","journal-title":"Mol. Neurodegener."},{"issue":"8","key":"10.1016\/j.bbrc.2025.152335_bib12","doi-asserted-by":"crossref","first-page":"430","DOI":"10.1016\/j.tem.2023.05.002","article-title":"Apolipoprotein E in lipid metabolism and neurodegenerative disease","volume":"34","author":"Yang","year":"2023","journal-title":"Trends Endocrinol. Metabol.: TEM (Trends Endocrinol. Metab.)"},{"issue":"2","key":"10.1016\/j.bbrc.2025.152335_bib13","doi-asserted-by":"crossref","first-page":"205","DOI":"10.1016\/j.neuron.2020.10.008","article-title":"Apolipoprotein E: structural insights and links to alzheimer disease pathogenesis","volume":"109","author":"Chen","year":"2021","journal-title":"Neuron"},{"issue":"8","key":"10.1016\/j.bbrc.2025.152335_bib14","doi-asserted-by":"crossref","first-page":"1375","DOI":"10.1194\/jlr.R400004-JLR200","article-title":"Thematic review series: brain Lipids. Cholesterol metabolism in the central nervous system during early development and in the mature animal","volume":"45","author":"Dietschy","year":"2004","journal-title":"JLR (J. Lipid Res.)"},{"issue":"4","key":"10.1016\/j.bbrc.2025.152335_bib15","doi-asserted-by":"crossref","first-page":"338","DOI":"10.1016\/j.tcb.2023.09.004","article-title":"The cell biology of APOE in the brain","volume":"34","author":"Windham","year":"2024","journal-title":"Trends Cell Biol."},{"issue":"2","key":"10.1016\/j.bbrc.2025.152335_bib16","doi-asserted-by":"crossref","first-page":"194","DOI":"10.1038\/s41593-019-0566-1","article-title":"Lipid-droplet-accumulating microglia represent a dysfunctional and proinflammatory state in the aging brain","volume":"23","author":"Marschallinger","year":"2020","journal-title":"Nat. Neurosci."},{"key":"10.1016\/j.bbrc.2025.152335_bib17","doi-asserted-by":"crossref","first-page":"155","DOI":"10.1016\/j.bbi.2021.11.018","article-title":"Long-term high-fat diet consumption by mice throughout adulthood induces neurobehavioral alterations and hippocampal neuronal remodeling accompanied by augmented microglial lipid accumulation","volume":"100","author":"Zhuang","year":"2022","journal-title":"Brain Behav. Immun."},{"issue":"8","key":"10.1016\/j.bbrc.2025.152335_bib18","doi-asserted-by":"crossref","first-page":"1304","DOI":"10.1016\/j.neuron.2022.03.004","article-title":"ApoE Cascade Hypothesis in the pathogenesis of Alzheimer's disease and related dementias","volume":"110","author":"Martens","year":"2022","journal-title":"Neuron"},{"issue":"38","key":"10.1016\/j.bbrc.2025.152335_bib19","doi-asserted-by":"crossref","first-page":"11965","DOI":"10.1073\/pnas.1510011112","article-title":"Phospholipid dysregulation contributes to ApoE4-associated cognitive deficits in Alzheimer's disease pathogenesis","volume":"112","author":"Zhu","year":"2015","journal-title":"Proc. Natl. Acad. Sci. U. S. A"},{"issue":"1","key":"10.1016\/j.bbrc.2025.152335_bib20","doi-asserted-by":"crossref","first-page":"3416","DOI":"10.1038\/s41467-021-23762-0","article-title":"Phospholipids of APOE lipoproteins activate microglia in an isoform-specific manner in preclinical models of Alzheimer's disease","volume":"12","author":"Fitz","year":"2021","journal-title":"Nat. Commun."},{"issue":"1","key":"10.1016\/j.bbrc.2025.152335_bib21","doi-asserted-by":"crossref","first-page":"15","DOI":"10.1186\/s13024-025-00802-7","article-title":"Cellular senescence induced by cholesterol accumulation is mediated by lysosomal ABCA1 in APOE4 and AD","volume":"20","author":"Wang","year":"2025","journal-title":"Mol. Neurodegener."},{"issue":"13","key":"10.1016\/j.bbrc.2025.152335_bib22","doi-asserted-by":"crossref","first-page":"2213","DOI":"10.1016\/j.cell.2022.05.017","article-title":"Cholesterol and matrisome pathways dysregulated in astrocytes and microglia","volume":"185","author":"Tcw","year":"2022","journal-title":"Cell"},{"issue":"Pt 9","key":"10.1016\/j.bbrc.2025.152335_bib23","doi-asserted-by":"crossref","first-page":"1991","DOI":"10.1242\/jcs.02324","article-title":"The lipid composition of autophagic vacuoles regulates expression of multilamellar bodies","volume":"118","author":"Lajoie","year":"2005","journal-title":"J. Cell Sci."},{"issue":"10","key":"10.1016\/j.bbrc.2025.152335_bib24","doi-asserted-by":"crossref","DOI":"10.1016\/j.celrep.2023.113183","article-title":"ApoE4-dependent lysosomal cholesterol accumulation impairs mitochondrial homeostasis and oxidative phosphorylation in human astrocytes","volume":"42","author":"Lee","year":"2023","journal-title":"Cell Rep."},{"issue":"1","key":"10.1016\/j.bbrc.2025.152335_bib25","doi-asserted-by":"crossref","first-page":"163","DOI":"10.1093\/brain\/awy289","article-title":"Apolipoprotein E4 genotype compromises brain exosome production","volume":"142","author":"Peng","year":"2019","journal-title":"Brain: J. Neurol."},{"issue":"1","key":"10.1016\/j.bbrc.2025.152335_bib26","doi-asserted-by":"crossref","first-page":"113","DOI":"10.1016\/j.stem.2022.12.007","article-title":"A single-cell transcriptome atlas of glial diversity in the human hippocampus across the postnatal lifespan","volume":"30","author":"Su","year":"2023","journal-title":"Cell Stem Cell"},{"issue":"6","key":"10.1016\/j.bbrc.2025.152335_bib27","doi-asserted-by":"crossref","first-page":"957","DOI":"10.1016\/j.neuron.2021.01.005","article-title":"Astrocytic ApoE reprograms neuronal cholesterol metabolism and histone-acetylation-mediated memory","volume":"109","author":"Li","year":"2021","journal-title":"Neuron"},{"issue":"1","key":"10.1016\/j.bbrc.2025.152335_bib28","doi-asserted-by":"crossref","first-page":"35","DOI":"10.1186\/s13024-020-00382-8","article-title":"Sex-dependent calcium hyperactivity due to lysosomal-related dysfunction in astrocytes from APOE4 versus APOE3 gene targeted replacement mice","volume":"15","author":"Larramona-Arcas","year":"2020","journal-title":"Mol. Neurodegener."},{"issue":"4","key":"10.1016\/j.bbrc.2025.152335_bib29","doi-asserted-by":"crossref","DOI":"10.1083\/jcb.202305003","article-title":"APOE traffics to astrocyte lipid droplets and modulates triglyceride saturation and droplet size","volume":"223","author":"Windham","year":"2024","journal-title":"J. Cell Biol."},{"issue":"1","key":"10.1016\/j.bbrc.2025.152335_bib30","doi-asserted-by":"crossref","first-page":"13","DOI":"10.1186\/s13024-022-00516-0","article-title":"Selective reduction of astrocyte apoE3 and apoE4 strongly reduces A\u03b2 accumulation and plaque-related pathology in a mouse model of amyloidosis","volume":"17","author":"Mahan","year":"2022","journal-title":"Mol. Neurodegener."},{"issue":"10","key":"10.1016\/j.bbrc.2025.152335_bib31","doi-asserted-by":"crossref","first-page":"1657","DOI":"10.1016\/j.neuron.2021.03.024","article-title":"Selective removal of astrocytic APOE4 strongly protects against tau-mediated neurodegeneration and decreases synaptic phagocytosis by microglia","volume":"109","author":"Wang","year":"2021","journal-title":"Neuron"},{"issue":"1","key":"10.1016\/j.bbrc.2025.152335_bib32","doi-asserted-by":"crossref","DOI":"10.1016\/j.celrep.2020.108572","article-title":"ApoE4 impairs neuron-astrocyte coupling of fatty acid metabolism","volume":"34","author":"Qi","year":"2021","journal-title":"Cell Rep."},{"issue":"15","key":"10.1016\/j.bbrc.2025.152335_bib33","doi-asserted-by":"crossref","first-page":"2363","DOI":"10.1016\/j.neuron.2021.07.013","article-title":"ApoE and immunity in Alzheimer's disease and related tauopathies: low-density lipoprotein receptor to the rescue","volume":"109","author":"Mendiola","year":"2021","journal-title":"Neuron"},{"issue":"6","key":"10.1016\/j.bbrc.2025.152335_bib34","doi-asserted-by":"crossref","first-page":"1141","DOI":"10.1016\/j.neuron.2018.05.008","article-title":"APOE4 causes widespread molecular and cellular alterations associated with Alzheimer's disease phenotypes in human iPSC-derived brain cell types","volume":"98","author":"Lin","year":"2018","journal-title":"Neuron"},{"issue":"1","key":"10.1016\/j.bbrc.2025.152335_bib35","doi-asserted-by":"crossref","first-page":"187","DOI":"10.1016\/j.cell.2024.10.027","article-title":"Decreased lipidated ApoE-receptor interactions confer protection against pathogenicity of ApoE and its lipid cargoes in lysosomes","volume":"188","author":"Guo","year":"2025","journal-title":"Cell"},{"issue":"15","key":"10.1016\/j.bbrc.2025.152335_bib36","doi-asserted-by":"crossref","first-page":"2413","DOI":"10.1016\/j.neuron.2021.05.034","article-title":"Overexpressing low-density lipoprotein receptor reduces tau-associated neurodegeneration in relation to apoE-linked mechanisms","volume":"109","author":"Shi","year":"2021","journal-title":"Neuron"},{"issue":"1","key":"10.1016\/j.bbrc.2025.152335_bib37","doi-asserted-by":"crossref","first-page":"37","DOI":"10.1186\/s13024-025-00825-0","article-title":"Decoding microglial immunometabolism: a new frontier in Alzheimer's disease research","volume":"20","author":"Jung","year":"2025","journal-title":"Mol. Neurodegener."},{"issue":"1","key":"10.1016\/j.bbrc.2025.152335_bib38","doi-asserted-by":"crossref","first-page":"75","DOI":"10.1186\/s13024-022-00577-1","article-title":"Opposing effects of apoE2 and apoE4 on microglial activation and lipid metabolism in response to demyelination","volume":"17","author":"Wang","year":"2022","journal-title":"Mol. Neurodegener."},{"issue":"1","key":"10.1016\/j.bbrc.2025.152335_bib39","doi-asserted-by":"crossref","first-page":"657","DOI":"10.1016\/j.apsb.2024.10.009","article-title":"Microglial APOE4 promotes neuron degeneration in Alzheimer's disease through inhibition of lipid droplet autophagy","volume":"15","author":"Mao","year":"2025","journal-title":"Acta Pharm. Sin. B"},{"issue":"8","key":"10.1016\/j.bbrc.2025.152335_bib40","doi-asserted-by":"crossref","first-page":"1197","DOI":"10.1016\/j.stem.2022.07.005","article-title":"Lipid accumulation induced by APOE4 impairs microglial surveillance of neuronal-network activity","volume":"29","author":"Victor","year":"2022","journal-title":"Cell Stem Cell"},{"issue":"11","key":"10.1016\/j.bbrc.2025.152335_bib41","doi-asserted-by":"crossref","first-page":"1839","DOI":"10.1038\/s41590-023-01627-6","article-title":"APOE4 impairs the microglial response in Alzheimer's disease by inducing TGF\u03b2-mediated checkpoints","volume":"24","author":"Yin","year":"2023","journal-title":"Nat. Immunol."},{"issue":"2","key":"10.1016\/j.bbrc.2025.152335_bib42","doi-asserted-by":"crossref","first-page":"106","DOI":"10.1038\/nrneurol.2012.263","article-title":"Apolipoprotein E and Alzheimer disease: risk, mechanisms and therapy","volume":"9","author":"Liu","year":"2013","journal-title":"Nat. Rev. Neurol."},{"issue":"2","key":"10.1016\/j.bbrc.2025.152335_bib43","doi-asserted-by":"crossref","first-page":"202","DOI":"10.1016\/j.neuron.2022.10.022","article-title":"TREM2-independent microgliosis promotes tau-mediated neurodegeneration in the presence of ApoE4","volume":"111","author":"Gratuze","year":"2023","journal-title":"Neuron"},{"issue":"3","key":"10.1016\/j.bbrc.2025.152335_bib44","doi-asserted-by":"crossref","first-page":"566","DOI":"10.1016\/j.immuni.2017.08.008","article-title":"The TREM2-APOE pathway drives the transcriptional phenotype of dysfunctional microglia in neurodegenerative diseases","volume":"47","author":"Krasemann","year":"2017","journal-title":"Immunity"},{"issue":"1","key":"10.1016\/j.bbrc.2025.152335_bib45","doi-asserted-by":"crossref","first-page":"50","DOI":"10.1186\/s13024-021-00473-0","article-title":"Plaque-associated human microglia accumulate lipid droplets in a chimeric model of Alzheimer's disease","volume":"16","author":"Claes","year":"2021","journal-title":"Mol. Neurodegener."},{"issue":"11","key":"10.1016\/j.bbrc.2025.152335_bib46","doi-asserted-by":"crossref","first-page":"1788","DOI":"10.1016\/j.neuron.2022.03.008","article-title":"Astrocytes and oligodendrocytes undergo subtype-specific transcriptional changes in Alzheimer's disease","volume":"110","author":"Sadick","year":"2022","journal-title":"Neuron"},{"issue":"6","key":"10.1016\/j.bbrc.2025.152335_bib47","doi-asserted-by":"crossref","first-page":"404","DOI":"10.1016\/j.tem.2016.03.018","article-title":"LXR regulation of brain cholesterol: from development to disease","volume":"27","author":"Courtney","year":"2016","journal-title":"Trends Endocrinol. Metabol.: TEM (Trends Endocrinol. Metab.)"},{"key":"10.1016\/j.bbrc.2025.152335_bib48","article-title":"The function of sphingolipids in different pathogenesis of Alzheimer's disease: a comprehensive review","volume":"171","author":"Wang","year":"2024","journal-title":"Biomedicine & Pharmacotherapy = Biomedecine & Pharmacotherapie"},{"issue":"6725","key":"10.1016\/j.bbrc.2025.152335_bib49","doi-asserted-by":"crossref","DOI":"10.1126\/science.adk7844","article-title":"Tlr7 drives sex differences in age- and Alzheimer's disease-related demyelination","volume":"386","author":"Lopez-Lee","year":"2024","journal-title":"Science (New York, N.Y.)"},{"issue":"11","key":"10.1016\/j.bbrc.2025.152335_bib50","doi-asserted-by":"crossref","first-page":"2138","DOI":"10.1038\/s41593-024-01757-6","article-title":"A cell-autonomous role for border-associated macrophages in ApoE4 neurovascular dysfunction and susceptibility to white matter injury","volume":"27","author":"Anfray","year":"2024","journal-title":"Nat. Neurosci."},{"issue":"3","key":"10.1016\/j.bbrc.2025.152335_bib51","doi-asserted-by":"crossref","first-page":"275","DOI":"10.1038\/s43587-023-00368-3","article-title":"Neuronal APOE4 removal protects against tau-mediated gliosis, neurodegeneration and myelin deficits","volume":"3","author":"Koutsodendris","year":"2023","journal-title":"Nature Aging"},{"issue":"3","key":"10.1016\/j.bbrc.2025.152335_bib52","doi-asserted-by":"crossref","first-page":"363","DOI":"10.1016\/j.stem.2018.12.013","article-title":"Cholesterol metabolism is a druggable Axis that independently regulates tau and amyloid-b in iPSCDerived Alzheimer's disease neurons","volume":"24","author":"van der Kant","year":"2019","journal-title":"Cell Stem Cell"},{"issue":"1","key":"10.1016\/j.bbrc.2025.152335_bib53","doi-asserted-by":"crossref","first-page":"74","DOI":"10.1002\/alz.13387","article-title":"Distinct transcriptomic responses to A\u03b2 plaques, neurofibrillary tangles, and APOE in Alzheimer's disease","volume":"20","author":"Das","year":"2024","journal-title":"Alzheimer's Dement.: The Journal of the Alzheimer's Association"},{"issue":"22","key":"10.1016\/j.bbrc.2025.152335_bib54","doi-asserted-by":"crossref","first-page":"3616","DOI":"10.3390\/cells11223616","article-title":"Lipid dys-homeostasis contributes to APOE4-associated AD pathology","volume":"11","author":"Lazar","year":"2022","journal-title":"Cells"},{"issue":"20","key":"10.1016\/j.bbrc.2025.152335_bib55","doi-asserted-by":"crossref","first-page":"4260","DOI":"10.1016\/j.cell.2023.08.021","article-title":"Alzheimer's disease: from immunotherapy to immunoprevention","volume":"186","author":"Jucker","year":"2023","journal-title":"Cell"},{"issue":"1","key":"10.1016\/j.bbrc.2025.152335_bib56","doi-asserted-by":"crossref","first-page":"24","DOI":"10.1186\/s13024-024-00714-y","article-title":"APOE4 genotype and aging impair injury-induced microglial behavior in brain slices, including toward A\u03b2, through P2RY12","volume":"19","author":"Sepulveda","year":"2024","journal-title":"Mol. Neurodegener."},{"issue":"36","key":"10.1016\/j.bbrc.2025.152335_bib57","doi-asserted-by":"crossref","first-page":"26326","DOI":"10.1074\/jbc.M611687200","article-title":"Partial reduction of BACE1 has dramatic effects on Alzheimer plaque and synaptic pathology in APP Transgenic Mice","volume":"282","author":"McConlogue","year":"2007","journal-title":"J. Biol. Chem."},{"issue":"2","key":"10.1016\/j.bbrc.2025.152335_bib58","doi-asserted-by":"crossref","first-page":"175","DOI":"10.1016\/j.ncl.2017.01.001","article-title":"Tau spread, apolipoprotein E, inflammation, and more: rapidly evolving basic science in alzheimer disease","volume":"35","author":"Gonzalez","year":"2017","journal-title":"Neurol. Clin."},{"issue":"1","key":"10.1016\/j.bbrc.2025.152335_bib59","doi-asserted-by":"crossref","first-page":"5540","DOI":"10.1038\/s41467-020-19264-0","article-title":"APOE4 exacerbates synapse loss and neurodegeneration in Alzheimer's disease patient iPSC-derived cerebral organoids","volume":"11","author":"Zhao","year":"2020","journal-title":"Nat. Commun."},{"issue":"10","key":"10.1016\/j.bbrc.2025.152335_bib60","doi-asserted-by":"crossref","first-page":"1124","DOI":"10.1001\/jamaneurol.2015.1721","article-title":"Characterizing apolipoprotein E \u03b54 carriers and noncarriers with the clinical diagnosis of mild to moderate alzheimer dementia and minimal \u03b2-amyloid peptide plaques","volume":"72","author":"Monsell","year":"2015","journal-title":"JAMA Neurol."},{"issue":"2","key":"10.1016\/j.bbrc.2025.152335_bib61","doi-asserted-by":"crossref","DOI":"10.1002\/alz.14625","article-title":"Tau-related reduction of glucose metabolism in mild cognitive impairment occurs independently of APOE \u03b54 genotype and is influenced by A\u03b2","volume":"21","author":"Carbonell","year":"2025","journal-title":"Alzheimer's Dement.: The Journal of the Alzheimer's Association"},{"key":"10.1016\/j.bbrc.2025.152335_bib62","doi-asserted-by":"crossref","DOI":"10.1093\/brain\/awaf016","article-title":"APOE4 impact on soluble and insoluble tau pathology is mostly influenced by amyloid-beta","author":"Cicognola","year":"2025","journal-title":"Brain: J. Neurol."},{"issue":"1","key":"10.1016\/j.bbrc.2025.152335_bib63","doi-asserted-by":"crossref","first-page":"91","DOI":"10.1007\/s00401-024-02744-8","article-title":"The influence of APOE\u03b54 on the pTau interactome in sporadic Alzheimer's disease","volume":"147","author":"Thierry","year":"2024","journal-title":"Acta Neuropathol."},{"issue":"3","key":"10.1016\/j.bbrc.2025.152335_bib64","doi-asserted-by":"crossref","DOI":"10.1002\/alz.14602","article-title":"Exploring epidemiological risk factors for cerebral amyloid angiopathy: considerations for monoclonal antibody therapy in people with Alzheimer's disease","volume":"21","author":"Ma","year":"2025","journal-title":"Alzheimer's Dement.: The Journal of the Alzheimer's Association"},{"issue":"6","key":"10.1016\/j.bbrc.2025.152335_bib65","doi-asserted-by":"crossref","first-page":"786","DOI":"10.1038\/s41593-021-00851-3","article-title":"Neuronal ApoE upregulates MHC-I expression to drive selective neurodegeneration in Alzheimer's disease","volume":"24","author":"Zalocusky","year":"2021","journal-title":"Nat. Neurosci."},{"issue":"7","key":"10.1016\/j.bbrc.2025.152335_bib66","doi-asserted-by":"crossref","first-page":"1170","DOI":"10.1038\/s41593-023-01352-1","article-title":"\u03b22-Microglobulin coaggregates with A\u03b2 and contributes to amyloid pathology and cognitive deficits in Alzheimer's disease model mice","volume":"26","author":"Zhao","year":"2023","journal-title":"Nat. Neurosci."},{"issue":"4","key":"10.1016\/j.bbrc.2025.152335_bib67","doi-asserted-by":"crossref","first-page":"657","DOI":"10.1002\/ana.27149","article-title":"Inhibition of bone morphogenetic protein signaling prevents tau pathology in iPSC derived neurons and PS19 mice","volume":"97","author":"Affaneh","year":"2025","journal-title":"Ann. Neurol."},{"issue":"34","key":"10.1016\/j.bbrc.2025.152335_bib68","doi-asserted-by":"crossref","DOI":"10.1073\/pnas.2108870119","article-title":"Astrocyte-secreted glypican-4 drives APOE4-dependent tau hyperphosphorylation","volume":"119","author":"Saroja","year":"2022","journal-title":"Proc. Natl. Acad. Sci. U. S. A"},{"issue":"1","key":"10.1016\/j.bbrc.2025.152335_bib69","doi-asserted-by":"crossref","first-page":"86","DOI":"10.1016\/j.stem.2024.10.005","article-title":"Microglia depletion reduces human neuronal APOE4-related pathologies in a chimeric Alzheimer's disease model","volume":"32","author":"Rao","year":"2025","journal-title":"Cell Stem Cell"},{"issue":"6","key":"10.1016\/j.bbrc.2025.152335_bib70","doi-asserted-by":"crossref","first-page":"524","DOI":"10.1016\/S1474-4422(25)00116-4","article-title":"Protective genetic variants against Alzheimer's disease","volume":"24","author":"Marino","year":"2025","journal-title":"Lancet Neurol."},{"issue":"2","key":"10.1016\/j.bbrc.2025.152335_bib71","doi-asserted-by":"crossref","first-page":"270","DOI":"10.1038\/s41591-018-0297-y","article-title":"Blood-brain barrier breakdown is an early biomarker of human cognitive dysfunction","volume":"25","author":"Nation","year":"2019","journal-title":"Nat. Med."},{"issue":"1","key":"10.1016\/j.bbrc.2025.152335_bib72","doi-asserted-by":"crossref","first-page":"270","DOI":"10.1172\/JCI115288","article-title":"Phenotypes of apolipoprotein B and apolipoprotein E after liver transplantation","volume":"88","author":"Linton","year":"1991","journal-title":"J. Clin. Investig."},{"issue":"1","key":"10.1016\/j.bbrc.2025.152335_bib73","doi-asserted-by":"crossref","first-page":"37","DOI":"10.1186\/s13024-019-0337-1","article-title":"Lack of hepatic apoE does not influence early A\u03b2 deposition: observations from a new APOE knock-in model","volume":"14","author":"Huynh","year":"2019","journal-title":"Mol. Neurodegener."},{"issue":"8","key":"10.1016\/j.bbrc.2025.152335_bib74","doi-asserted-by":"crossref","first-page":"1020","DOI":"10.1038\/s41593-022-01127-0","article-title":"Peripheral apoE4 enhances Alzheimer's pathology and impairs cognition by compromising cerebrovascular function","volume":"25","author":"Liu","year":"2022","journal-title":"Nat. Neurosci."},{"issue":"7806","key":"10.1016\/j.bbrc.2025.152335_bib75","doi-asserted-by":"crossref","first-page":"71","DOI":"10.1038\/s41586-020-2247-3","article-title":"APOE4 leads to blood-brain barrier dysfunction predicting cognitive decline","volume":"581","author":"Montagne","year":"2020","journal-title":"Nature"},{"issue":"3","key":"10.1016\/j.bbrc.2025.152335_bib76","doi-asserted-by":"crossref","first-page":"243","DOI":"10.1038\/s43587-021-00043-5","article-title":"Healthy aging and the blood-brain barrier","volume":"1","author":"Banks","year":"2021","journal-title":"Nature Aging"},{"key":"10.1016\/j.bbrc.2025.152335_bib77","doi-asserted-by":"crossref","DOI":"10.1016\/j.ebiom.2024.105487","article-title":"Impacts of APOE-\u03b54 and exercise training on brain microvascular endothelial cell barrier function and metabolism","volume":"111","author":"Weber","year":"2025","journal-title":"EBioMedicine"},{"issue":"1","key":"10.1016\/j.bbrc.2025.152335_bib78","doi-asserted-by":"crossref","first-page":"34","DOI":"10.1186\/s12979-022-00289-6","article-title":"Aged microglia promote peripheral T cell infiltration by reprogramming the microenvironment of neurogenic niches","volume":"19","author":"Zhang","year":"2022","journal-title":"Immun. Ageing: Ir. Am."},{"issue":"11","key":"10.1016\/j.bbrc.2025.152335_bib79","doi-asserted-by":"crossref","DOI":"10.1084\/jem.20221137","article-title":"A \"multi-omics\" analysis of blood-brain barrier and synaptic dysfunction in APOE4 mice","volume":"219","author":"Barisano","year":"2022","journal-title":"J. Exp. Med."},{"issue":"6","key":"10.1016\/j.bbrc.2025.152335_bib80","doi-asserted-by":"crossref","first-page":"506","DOI":"10.1038\/s43587-021-00073-z","article-title":"APOE4 accelerates advanced-stage vascular and neurodegenerative disorder in old Alzheimer's mice via cyclophilin A independently of amyloid-\u03b2","volume":"1","author":"Montagne","year":"2021","journal-title":"Nature Aging"},{"issue":"6","key":"10.1016\/j.bbrc.2025.152335_bib81","doi-asserted-by":"crossref","DOI":"10.1212\/WNL.0000000000213441","article-title":"Effect modifiers of the association of blood pressure with brain amyloid and tau pathology","volume":"104","author":"Cai","year":"2025","journal-title":"Neurology"},{"issue":"19","key":"10.1016\/j.bbrc.2025.152335_bib82","doi-asserted-by":"crossref","first-page":"e2092","DOI":"10.1212\/WNL.0000000000201019","article-title":"Incidence of amyloid-related imaging abnormalities in patients with alzheimer disease treated with anti-\u03b2-amyloid immunotherapy: a meta-analysis","volume":"99","author":"Jeong","year":"2022","journal-title":"Neurology"},{"issue":"3","key":"10.1016\/j.bbrc.2025.152335_bib83","doi-asserted-by":"crossref","DOI":"10.1212\/WNL.0000000000207919","article-title":"Genome-wide association studies of ARIA from the Aducanumab phase 3 ENGAGE and EMERGE studies","volume":"102","author":"Loomis","year":"2024","journal-title":"Neurology"},{"issue":"1","key":"10.1016\/j.bbrc.2025.152335_bib84","article-title":"Lecanemab in early Alzheimer's disease","volume":"388","author":"Ch","year":"2023","journal-title":"N. Engl. J. Med."},{"issue":"16","key":"10.1016\/j.bbrc.2025.152335_bib85","doi-asserted-by":"crossref","first-page":"6826","DOI":"10.7150\/thno.72685","article-title":"A sporadic Alzheimer's blood-brain barrier model for developing ultrasound-mediated delivery of Aducanumab and anti-Tau antibodies","volume":"12","author":"Wasielewska","year":"2022","journal-title":"Theranostics"},{"key":"10.1016\/j.bbrc.2025.152335_bib86","doi-asserted-by":"crossref","DOI":"10.1016\/j.arr.2024.102620","article-title":"Monoclonal therapy with lecanemab in the treatment of mild Alzheimer's disease: a systematic review and meta-analysis","volume":"104","author":"Arroyo-Pacheco","year":"2025","journal-title":"Ageing Res. Rev."},{"issue":"5","key":"10.1016\/j.bbrc.2025.152335_bib87","doi-asserted-by":"crossref","first-page":"431","DOI":"10.1001\/jamaneurol.2023.0207","article-title":"Lecanemab and APOE genotyping in clinical practice-navigating uncharted terrain","volume":"80","author":"Thambisetty","year":"2023","journal-title":"JAMA Neurol."},{"issue":"3","key":"10.1016\/j.bbrc.2025.152335_bib88","first-page":"149","article-title":"Clinical effects of tramiprosate in APOE4\/4 homozygous patients with mild Alzheimer's disease suggest disease modification potential","volume":"4","author":"Abushakra","year":"2017","journal-title":"The Journal of Prevention of Alzheimer's Disease"},{"issue":"1","key":"10.1016\/j.bbrc.2025.152335_bib89","doi-asserted-by":"crossref","first-page":"88","DOI":"10.1186\/s13195-022-01020-9","article-title":"Imipramine and olanzapine block apoE4-catalyzed polymerization of A\u03b2 and show evidence of improving Alzheimer's disease cognition","volume":"14","author":"Johnson","year":"2022","journal-title":"Alzheimers Res. Ther."},{"issue":"1","key":"10.1016\/j.bbrc.2025.152335_bib90","doi-asserted-by":"crossref","first-page":"10","DOI":"10.1186\/s13195-017-0237-y","article-title":"Evidence for benefit of statins to modify cognitive decline and risk in Alzheimer's disease","volume":"9","author":"Geifman","year":"2017","journal-title":"Alzheimers Res. Ther."},{"issue":"7937","key":"10.1016\/j.bbrc.2025.152335_bib91","doi-asserted-by":"crossref","first-page":"769","DOI":"10.1038\/s41586-022-05439-w","article-title":"APOE4 impairs myelination via cholesterol dysregulation in oligodendrocytes","volume":"611","author":"Blanchard","year":"2022","journal-title":"Nature"},{"issue":"1","key":"10.1016\/j.bbrc.2025.152335_bib92","doi-asserted-by":"crossref","first-page":"1121","DOI":"10.1038\/s41467-022-28769-9","article-title":"ATAD3A oligomerization promotes neuropathology and cognitive deficits in Alzheimer's disease models","volume":"13","author":"Zhao","year":"2022","journal-title":"Nat. Commun."},{"issue":"4","key":"10.1016\/j.bbrc.2025.152335_bib93","doi-asserted-by":"crossref","DOI":"10.1126\/sciadv.adj1354","article-title":"CYP46A1-mediated cholesterol turnover induces sex-specific changes in cognition and counteracts memory loss in ovariectomized mice","volume":"10","author":"Latorre-Leal","year":"2024","journal-title":"Sci. Adv."},{"issue":"7","key":"10.1016\/j.bbrc.2025.152335_bib94","doi-asserted-by":"crossref","first-page":"1701","DOI":"10.1007\/s00415-012-6690-4","article-title":"CYP46A1 T\/C polymorphism associated with the APOE \u03b54 allele increases the risk of Alzheimer's disease","volume":"260","author":"Li","year":"2013","journal-title":"J. Neurol."},{"issue":"3","key":"10.1016\/j.bbrc.2025.152335_bib95","doi-asserted-by":"crossref","first-page":"1219","DOI":"10.3233\/JAD-160467","article-title":"ABCA1 agonist reverses the ApoE4-driven cognitive and brain pathologies","volume":"54","author":"Boehm-Cagan","year":"2016","journal-title":"J. Alzheim. Dis.: JAD"},{"issue":"20","key":"10.1016\/j.bbrc.2025.152335_bib96","doi-asserted-by":"crossref","first-page":"6862","DOI":"10.1523\/JNEUROSCI.1051-10.2010","article-title":"Liver X receptor agonist treatment ameliorates amyloid pathology and memory deficits caused by high-fat diet in APP23 mice","volume":"30","author":"Fitz","year":"2010","journal-title":"J. Neurosci.: The Official Journal of the Society for Neuroscience"},{"issue":"3","key":"10.1016\/j.bbrc.2025.152335_bib97","doi-asserted-by":"crossref","first-page":"384","DOI":"10.1016\/j.neuron.2023.10.023","article-title":"Amelioration of Tau and ApoE4-linked glial lipid accumulation and neurodegeneration with an LXR agonist","volume":"112","author":"Litvinchuk","year":"2024","journal-title":"Neuron"},{"issue":"583","key":"10.1016\/j.bbrc.2025.152335_bib98","doi-asserted-by":"crossref","DOI":"10.1126\/scitranslmed.aaz4564","article-title":"APOE4 disrupts intracellular lipid homeostasis in human iPSC-derived glia","volume":"13","author":"Sienski","year":"2021","journal-title":"Sci. Transl. Med."},{"issue":"7","key":"10.1016\/j.bbrc.2025.152335_bib99","doi-asserted-by":"crossref","first-page":"1305","DOI":"10.1161\/ATVBAHA.116.307023","article-title":"Central nervous system lipoproteins: ApoE and regulation of cholesterol metabolism","volume":"36","author":"Mahley","year":"2016","journal-title":"Arterioscler. Thromb. Vasc. Biol."},{"issue":"8006","key":"10.1016\/j.bbrc.2025.152335_bib100","doi-asserted-by":"crossref","first-page":"154","DOI":"10.1038\/s41586-024-07185-7","article-title":"APOE4\/4 is linked to damaging lipid droplets in Alzheimer's disease microglia","volume":"628","author":"Haney","year":"2024","journal-title":"Nature"},{"issue":"1","key":"10.1016\/j.bbrc.2025.152335_bib101","doi-asserted-by":"crossref","first-page":"52","DOI":"10.1186\/s40035-024-00445-6","article-title":"TRPV1 alleviates APOE4-dependent microglial antigen presentation and T cell infiltration in Alzheimer's disease","volume":"13","author":"Lu","year":"2024","journal-title":"Transl. Neurodegener."},{"issue":"2","key":"10.1016\/j.bbrc.2025.152335_bib102","doi-asserted-by":"crossref","first-page":"347","DOI":"10.1038\/s12276-023-00935-z","article-title":"TRPV1 regulates ApoE4-disrupted intracellular lipid homeostasis and decreases synaptic phagocytosis by microglia","volume":"55","author":"Wang","year":"2023","journal-title":"Exp. Mol. Med."},{"key":"10.1016\/j.bbrc.2025.152335_bib103","doi-asserted-by":"crossref","first-page":"2990","DOI":"10.1038\/s41591-024-03122-3","article-title":"Sex-dependent APOE4 neutrophil-microglia interactions drive cognitive impairment in Alzheimer\u2019s disease","volume":"30","author":"Rosenzweig","year":"2024","journal-title":"Nat. Med."},{"issue":"2","key":"10.1016\/j.bbrc.2025.152335_bib104","doi-asserted-by":"crossref","first-page":"116","DOI":"10.1038\/s41422-022-00759-y","article-title":"LilrB3 is a putative cell surface receptor of APOE4","volume":"33","author":"Zhou","year":"2023","journal-title":"Cell Res."},{"issue":"4","key":"10.1016\/j.bbrc.2025.152335_bib105","doi-asserted-by":"crossref","first-page":"2632","DOI":"10.1002\/alz.13703","article-title":"Silencing Apoe with divalent-siRNAs improves amyloid burden and activates immune response pathways in Alzheimer's disease","volume":"20","author":"Ferguson","year":"2024","journal-title":"Alzheimer's Dement.: The Journal of the Alzheimer's Association"},{"issue":"4","key":"10.1016\/j.bbrc.2025.152335_bib106","doi-asserted-by":"crossref","first-page":"406","DOI":"10.1038\/s41419-022-04858-x","article-title":"Ageing related thyroid deficiency increases brain-targeted transport of liver-derived ApoE4-laden exosomes leading to cognitive impairment","volume":"13","author":"Zhang","year":"2022","journal-title":"Cell Death Dis."},{"issue":"1","key":"10.1016\/j.bbrc.2025.152335_bib107","first-page":"24","article-title":"AAVrh.10-Mediated APOE2 central nervous system gene therapy for APOE4-associated Alzheimer's disease, human gene therapy","volume":"29","author":"Rosenberg","year":"2018","journal-title":"Clinical Development"},{"issue":"12","key":"10.1016\/j.bbrc.2025.152335_bib108","doi-asserted-by":"crossref","first-page":"2104","DOI":"10.1038\/s41593-023-01480-8","article-title":"The APOE-R136S mutation protects against APOE4-driven Tau pathology, neurodegeneration and neuroinflammation","volume":"26","author":"Nelson","year":"2023","journal-title":"Nat. Neurosci."},{"issue":"2","key":"10.1016\/j.bbrc.2025.152335_bib109","doi-asserted-by":"crossref","first-page":"428","DOI":"10.1016\/j.cell.2023.11.029","article-title":"APOE3ch alters microglial response and suppresses A\u03b2-induced tau seeding and spread","volume":"187","author":"Chen","year":"2024","journal-title":"Cell"},{"issue":"8000","key":"10.1016\/j.bbrc.2025.152335_bib110","doi-asserted-by":"crossref","first-page":"881","DOI":"10.1038\/s41586-023-06984-8","article-title":"An epigenetic barrier sets the timing of human neuronal maturation","volume":"626","author":"Ciceri","year":"2024","journal-title":"Nature"},{"issue":"3","key":"10.1016\/j.bbrc.2025.152335_bib111","doi-asserted-by":"crossref","first-page":"161","DOI":"10.1038\/nrd4570","article-title":"What does it take to produce a breakthrough drug?","volume":"14","author":"Calcoen","year":"2015","journal-title":"Nat. Rev. Drug Discov."}],"container-title":["Biochemical and Biophysical Research Communications"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S0006291X25010502?httpAccept=text\/xml","content-type":"text\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S0006291X25010502?httpAccept=text\/plain","content-type":"text\/plain","content-version":"vor","intended-application":"text-mining"}],"deposited":{"date-parts":[[2026,4,29]],"date-time":"2026-04-29T11:17:58Z","timestamp":1777461478000},"score":1,"resource":{"primary":{"URL":"https:\/\/linkinghub.elsevier.com\/retrieve\/pii\/S0006291X25010502"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,9]]},"references-count":111,"alternative-id":["S0006291X25010502"],"URL":"https:\/\/doi.org\/10.1016\/j.bbrc.2025.152335","relation":{},"ISSN":["0006-291X"],"issn-type":[{"value":"0006-291X","type":"print"}],"subject":[],"published":{"date-parts":[[2025,9]]},"assertion":[{"value":"Elsevier","name":"publisher","label":"This article is maintained by"},{"value":"APOE4-driven lipid metabolic dysregulation in Alzheimer's disease: Multi-pathway mechanisms and therapeutic perspectives","name":"articletitle","label":"Article Title"},{"value":"Biochemical and Biophysical Research Communications","name":"journaltitle","label":"Journal Title"},{"value":"https:\/\/doi.org\/10.1016\/j.bbrc.2025.152335","name":"articlelink","label":"CrossRef DOI link to publisher maintained version"},{"value":"article","name":"content_type","label":"Content Type"},{"value":"\u00a9 2025 Elsevier Inc. All rights are reserved, including those for text and data mining, AI training, and similar technologies.","name":"copyright","label":"Copyright"}],"article-number":"152335"}}