{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,5]],"date-time":"2026-10-05T14:03:58Z","timestamp":1791209038290,"version":"4.1.0"},"reference-count":131,"publisher":"Wiley","license":[{"start":{"date-parts":[[2026,10,5]],"date-time":"2026-10-05T00:00:00Z","timestamp":1791158400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"},{"start":{"date-parts":[[2026,10,5]],"date-time":"2026-10-05T00:00:00Z","timestamp":1791158400000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/100000968","name":"American Heart Association","doi-asserted-by":"publisher","award":["24TPA1288391"],"award-info":[{"award-number":["24TPA1288391"]}],"id":[{"id":"10.13039\/100000968","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["febs.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["The FEBS Journal"],"abstract":"<jats:p>\n                    The apolipoprotein E \u03b54 (\n                    <jats:italic>APOE4<\/jats:italic>\n                    ) allele is the strongest common genetic risk factor for late\u2010onset Alzheimer's disease. However, its incomplete penetrance supports the view that it acts as a modifiable systems\u2010level perturbation of brain homeostasis rather than a deterministic driver. Increasing evidence further positions APOE4 protein within interconnected lipid metabolic pathways, with converging genetic, epidemiological, and translational studies implicating disrupted cholesterol transport, lipoprotein metabolism, and lipid oxidation as upstream mechanisms that promote neurodegeneration. Here, we synthesize currently developing therapeutic strategies targeting APOE4 across domains: small molecules, endogenous protectors, emerging biologics, and systemic lipid modulators. Small molecules include structural correctors and natural compounds, while endogenous protection arises from APOE2, the APOE3\u2010Christchurch variant, and modifiers such as CASP7, KLOTHO, the VHL\u2013HIF axis, fibronectin, and NHE6\u2010mediated endosomal regulation. Biologic platforms enable allele\u2010selective and pathway\u2010specific interventions via siRNA, antisense oligonucleotides, and antibodies targeting pathological APOE conformers. In parallel, cholesteryl ester transfer protein (CETP) inhibition has emerged as a systems\u2010level strategy that restores lipid and redox homeostasis, with early clinical evidence showing reductions in neurodegenerative biomarkers, particularly in APOE4 carriers. These advances support an integrative therapeutic framework to restore brain lipid homeostasis, stress resilience and neural\u2013vascular coupling, positioning APOE4 as a modifiable node within a preventable lipid\u2013vascular\u2013neurodegenerative axis.\n                  <\/jats:p>","DOI":"10.1111\/febs.70759","type":"journal-article","created":{"date-parts":[[2026,10,5]],"date-time":"2026-10-05T13:14:38Z","timestamp":1791206078000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Emerging therapeutic strategies to target\n                    <scp>APOE4<\/scp>\n                    in Alzheimer's disease"],"prefix":"10.1111","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-6394-635X","authenticated-orcid":false,"given":"Wei I.","family":"Jiang","sequence":"first","affiliation":[{"name":"College of Life Sciences and Oceanography Shenzhen University  Shenzhen Guangdong China"},{"name":"Cardiovascular Research Institute University of California San Francisco  CA USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bingying","family":"Wang","sequence":"additional","affiliation":[{"name":"Cardiovascular Research Institute University of California San Francisco  CA USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5619-7485","authenticated-orcid":false,"given":"Dengke K.","family":"Ma","sequence":"additional","affiliation":[{"name":"Cardiovascular Research Institute University of California San Francisco  CA USA"},{"name":"Department of Physiology University of California San Francisco  CA USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,10,5]]},"reference":[{"key":"e_1_2_8_2_1","doi-asserted-by":"crossref","first-page":"1977","DOI":"10.1073\/pnas.90.5.1977","article-title":"Apolipoprotein E: high\u2010avidity binding to beta\u2010amyloid and increased frequency of type 4 allele in late\u2010onset familial Alzheimer disease","volume":"90","author":"Strittmatter WJ","year":"1993","journal-title":"Proc Natl Acad Sci USA"},{"key":"e_1_2_8_3_1","doi-asserted-by":"crossref","first-page":"921","DOI":"10.1126\/science.8346443","article-title":"Gene dose of apolipoprotein E type 4 allele and the risk of Alzheimer's disease in late onset families","volume":"261","author":"Corder EH","year":"1993","journal-title":"Science"},{"key":"e_1_2_8_4_1","doi-asserted-by":"crossref","first-page":"1349","DOI":"10.1001\/jama.1997.03550160069041","article-title":"Effects of age, sex, and ethnicity on the association between apolipoprotein E genotype and Alzheimer disease. A meta\u2010analysis. APOE and Alzheimer disease meta analysis consortium","volume":"278","author":"Farrer LA","year":"1997","journal-title":"JAMA"},{"key":"e_1_2_8_5_1","doi-asserted-by":"crossref","first-page":"625","DOI":"10.1002\/ana.26864","article-title":"Report of the APOE4 National Institute on Aging\/Alzheimer disease sequencing project consortium working group: reducing APOE4 in carriers is a therapeutic goal for Alzheimer's disease","volume":"95","author":"Vance JM","year":"2024","journal-title":"Ann Neurol"},{"key":"e_1_2_8_6_1","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 J","year":"2024","journal-title":"Nat Med"},{"key":"e_1_2_8_7_1","doi-asserted-by":"crossref","first-page":"501","DOI":"10.1038\/s41582-019-0228-7","article-title":"Apolipoprotein E and Alzheimer disease: pathobiology and targeting strategies","volume":"15","author":"Yamazaki Y","year":"2019","journal-title":"Nat Rev Neurol"},{"key":"e_1_2_8_8_1","doi-asserted-by":"crossref","first-page":"903","DOI":"10.1038\/mp.2011.52","article-title":"APOE and Alzheimer disease: a major gene with semi\u2010dominant inheritance","volume":"16","author":"Genin E","year":"2011","journal-title":"Mol Psychiatry"},{"key":"e_1_2_8_9_1","doi-asserted-by":"crossref","first-page":"91","DOI":"10.1038\/s41583-023-00776-9","article-title":"Cell type\u2010specific roles of APOE4 in Alzheimer disease","volume":"25","author":"Blumenfeld J","year":"2024","journal-title":"Nat Rev Neurosci"},{"key":"e_1_2_8_10_1","doi-asserted-by":"crossref","first-page":"457","DOI":"10.1038\/s41582-024-00988-2","article-title":"Multifaceted roles of APOE in Alzheimer disease","volume":"20","author":"Jackson RJ","year":"2024","journal-title":"Nat Rev Neurol"},{"key":"e_1_2_8_11_1","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 IA","year":"2024","journal-title":"Trends Cell Biol"},{"key":"e_1_2_8_12_1","doi-asserted-by":"crossref","first-page":"11587","DOI":"10.1073\/pnas.201279298","article-title":"Introduction of human apolipoprotein E4 \u201cdomain interaction\u201d into mouse apolipoprotein E","volume":"98","author":"Raffai RL","year":"2001","journal-title":"Proc Natl Acad Sci USA"},{"key":"e_1_2_8_13_1","doi-asserted-by":"crossref","first-page":"2498","DOI":"10.1002\/jnr.22073","article-title":"Mechanism underlying apolipoprotein E (ApoE) isoform\u2010dependent lipid efflux from neural cells in culture","volume":"87","author":"Minagawa H","year":"2009","journal-title":"J Neurosci Res"},{"key":"e_1_2_8_14_1","doi-asserted-by":"crossref","first-page":"17217","DOI":"10.1074\/jbc.M110.217380","article-title":"Structure\u2010dependent impairment of intracellular apolipoprotein E4 trafficking and its detrimental effects are rescued by small\u2010molecule structure correctors","volume":"286","author":"Brodbeck J","year":"2011","journal-title":"J Biol Chem"},{"key":"e_1_2_8_15_1","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 JW","year":"2022","journal-title":"Nature"},{"key":"e_1_2_8_16_1","doi-asserted-by":"crossref","DOI":"10.1016\/j.celrep.2025.115961","article-title":"Triglyceride metabolism controls inflammation and microglial phenotypes associated with APOE4","volume":"44","author":"Stephenson RA","year":"2025","journal-title":"Cell Rep"},{"key":"e_1_2_8_17_1","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 MS","year":"2024","journal-title":"Nature"},{"key":"e_1_2_8_18_1","doi-asserted-by":"crossref","first-page":"18694","DOI":"10.1073\/pnas.0508254102","article-title":"Lipid\u2010 and receptor\u2010binding regions of apolipoprotein E4 fragments act in concert to cause mitochondrial dysfunction and neurotoxicity","volume":"102","author":"Chang S","year":"2005","journal-title":"Proc Natl Acad Sci USA"},{"key":"e_1_2_8_19_1","doi-asserted-by":"crossref","first-page":"14908","DOI":"10.3390\/ijms140714908","article-title":"Proteolytic cleavage of apolipoprotein E4 as the keystone for the heightened risk associated with Alzheimer's disease","volume":"14","author":"Rohn TT","year":"2013","journal-title":"Int J Mol Sci"},{"key":"e_1_2_8_20_1","doi-asserted-by":"crossref","first-page":"10966","DOI":"10.1073\/pnas.1434398100","article-title":"Carboxyl\u2010terminal\u2010truncated apolipoprotein E4 causes Alzheimer's disease\u2010like neurodegeneration and behavioral deficits in transgenic mice","volume":"100","author":"Harris FM","year":"2003","journal-title":"Proc Natl Acad Sci USA"},{"key":"e_1_2_8_21_1","doi-asserted-by":"crossref","unstructured":"KrogsaeterEK McKetneyJ LiL LiuI RichardsAL SubramanyamV YinK GordonM MairalPB StevensonEJet\u00a0al. (2026)APOE4 disrupts the central dogma by arresting neuronal proteome dynamics. 2026.07.15.738801.","DOI":"10.64898\/2026.07.15.738801"},{"key":"e_1_2_8_22_1","doi-asserted-by":"crossref","first-page":"523","DOI":"10.1038\/nature24016","article-title":"ApoE4 markedly exacerbates tau\u2010mediated neurodegeneration in a mouse model of tauopathy","volume":"549","author":"Shi Y","year":"2017","journal-title":"Nature"},{"key":"e_1_2_8_23_1","doi-asserted-by":"crossref","DOI":"10.1126\/scitranslmed.3002156","article-title":"Human apoE isoforms differentially regulate brain amyloid\u2010\u03b2 peptide clearance","volume":"3","author":"Castellano JM","year":"2011","journal-title":"Sci Transl Med"},{"key":"e_1_2_8_24_1","doi-asserted-by":"crossref","first-page":"4002","DOI":"10.1172\/JCI36663","article-title":"apoE isoform\u2010specific disruption of amyloid beta peptide clearance from mouse brain","volume":"118","author":"Deane R","year":"2008","journal-title":"J Clin Invest"},{"key":"e_1_2_8_25_1","doi-asserted-by":"crossref","first-page":"235","DOI":"10.1016\/0304-3940(92)90444-C","article-title":"Apolipoprotein E: a pathological chaperone protein in patients with cerebral and systemic amyloid","volume":"135","author":"Wisniewski T","year":"1992","journal-title":"Neurosci Lett"},{"key":"e_1_2_8_26_1","doi-asserted-by":"crossref","first-page":"1898","DOI":"10.1016\/j.neuron.2023.03.024","article-title":"Differential and substrate\u2010specific inhibition of \u03b3\u2010secretase by the C\u2010terminal region of ApoE2, ApoE3, and ApoE4","volume":"111","author":"Hou X","year":"2023","journal-title":"Neuron"},{"key":"e_1_2_8_27_1","doi-asserted-by":"crossref","first-page":"22529","DOI":"10.1074\/jbc.M801925200","article-title":"Direct and potent regulation of gamma\u2010secretase by its lipid microenvironment","volume":"283","author":"Osenkowski P","year":"2008","journal-title":"J Biol Chem"},{"key":"e_1_2_8_28_1","doi-asserted-by":"crossref","first-page":"11","DOI":"10.1006\/nbdi.2001.0470","article-title":"Cholesterol\u2010dependent gamma\u2010secretase activity in buoyant cholesterol\u2010rich membrane microdomains","volume":"9","author":"Wahrle S","year":"2002","journal-title":"Neurobiol Dis"},{"key":"e_1_2_8_29_1","doi-asserted-by":"crossref","DOI":"10.1016\/j.pneurobio.2021.102212","article-title":"Neuronal ApoE4 stimulates C\/EBP\u03b2 activation, promoting Alzheimer's disease pathology in a mouse model","volume":"209","author":"Wang Z\u2010H","year":"2022","journal-title":"Prog Neurobiol"},{"key":"e_1_2_8_30_1","doi-asserted-by":"crossref","first-page":"496","DOI":"10.1038\/s41591-018-0336-8","article-title":"ApoE attenuates unresolvable inflammation by complex formation with activated C1q","volume":"25","author":"Yin C","year":"2019","journal-title":"Nat Med"},{"key":"e_1_2_8_31_1","doi-asserted-by":"crossref","first-page":"328","DOI":"10.1016\/j.neuron.2016.06.015","article-title":"TREM2 binds to apolipoproteins, including APOE and CLU\/APOJ, and thereby facilitates uptake of amyloid\u2010Beta by microglia","volume":"91","author":"Yeh FL","year":"2016","journal-title":"Neuron"},{"key":"e_1_2_8_32_1","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 J","year":"2023","journal-title":"Cell Res"},{"key":"e_1_2_8_33_1","doi-asserted-by":"crossref","DOI":"10.3390\/cells14040243","article-title":"From genetics to neuroinflammation: the impact of ApoE4 on microglial function in Alzheimer's disease","volume":"14","author":"Dias D","year":"2025","journal-title":"Cells"},{"key":"e_1_2_8_34_1","doi-asserted-by":"crossref","first-page":"641","DOI":"10.5582\/bst.2025.01148","article-title":"APOE4 reprograms microglial lipid metabolism in Alzheimer's disease: mechanisms and therapeutic implications","volume":"19","author":"Chen J","year":"2026","journal-title":"Biosci Trends"},{"key":"e_1_2_8_35_1","doi-asserted-by":"crossref","first-page":"1276","DOI":"10.1016\/j.cell.2017.05.018","article-title":"A unique microglia type associated with restricting development of Alzheimer's disease","volume":"169","author":"Keren\u2010Shaul H","year":"2017","journal-title":"Cell"},{"key":"e_1_2_8_36_1","doi-asserted-by":"crossref","first-page":"71","DOI":"10.1038\/s41586-020-2247-3","article-title":"APOE4 leads to blood\u2010brain barrier dysfunction predicting cognitive decline","volume":"581","author":"Montagne A","year":"2020","journal-title":"Nature"},{"key":"e_1_2_8_37_1","doi-asserted-by":"crossref","first-page":"216","DOI":"10.1038\/jcbfm.2015.44","article-title":"Accelerated pericyte degeneration and blood\u2010brain barrier breakdown in apolipoprotein E4 carriers with Alzheimer's disease","volume":"36","author":"Halliday MR","year":"2016","journal-title":"J Cereb Blood Flow Metab"},{"key":"e_1_2_8_38_1","doi-asserted-by":"crossref","first-page":"512","DOI":"10.1038\/nature11087","article-title":"Apolipoprotein E controls cerebrovascular integrity via cyclophilin a","volume":"485","author":"Bell RD","year":"2012","journal-title":"Nature"},{"key":"e_1_2_8_39_1","doi-asserted-by":"crossref","first-page":"14069","DOI":"10.1523\/JNEUROSCI.2281-14.2014","article-title":"Apolipoprotein E4 produced in GABAergic interneurons causes learning and memory deficits in mice","volume":"34","author":"Knoferle J","year":"2014","journal-title":"J Neurosci"},{"key":"e_1_2_8_40_1","doi-asserted-by":"crossref","first-page":"24","DOI":"10.1186\/s13024-019-0324-6","article-title":"Apolipoprotein E4, inhibitory network dysfunction, and Alzheimer's disease","volume":"14","author":"Najm R","year":"2019","journal-title":"Mol Neurodegener"},{"key":"e_1_2_8_41_1","doi-asserted-by":"crossref","first-page":"12011","DOI":"10.1073\/pnas.0914984107","article-title":"ApoE4 reduces glutamate receptor function and synaptic plasticity by selectively impairing ApoE receptor recycling","volume":"107","author":"Chen Y","year":"2010","journal-title":"Proc Natl Acad Sci USA"},{"key":"e_1_2_8_42_1","doi-asserted-by":"crossref","DOI":"10.3390\/ijms252212029","article-title":"Therapeutic challenges derived from the interaction among apolipoprotein E, cholesterol, and amyloid in Alzheimer's disease","volume":"25","author":"Menendez\u2010Gonzalez M","year":"2024","journal-title":"Int J Mol Sci"},{"key":"e_1_2_8_43_1","doi-asserted-by":"crossref","first-page":"647","DOI":"10.1038\/s41591-018-0004-z","article-title":"Gain of toxic apolipoprotein E4 effects in human iPSC\u2010derived neurons is ameliorated by a small\u2010molecule structure corrector","volume":"24","author":"Wang C","year":"2018","journal-title":"Nat Med"},{"key":"e_1_2_8_44_1","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\u2010Pozo A","year":"2021","journal-title":"Lancet Neurol"},{"key":"e_1_2_8_45_1","doi-asserted-by":"crossref","first-page":"1503","DOI":"10.1126\/science.1217697","article-title":"ApoE\u2010directed therapeutics rapidly clear \u03b2\u2010amyloid and reverse deficits in AD mouse models","volume":"335","author":"Cramer PE","year":"2012","journal-title":"Science"},{"key":"e_1_2_8_46_1","doi-asserted-by":"crossref","first-page":"384","DOI":"10.1016\/j.neuron.2023.10.023","article-title":"Amelioration of tau and ApoE4\u2010linked glial lipid accumulation and neurodegeneration with an LXR agonist","volume":"112","author":"Litvinchuk A","year":"2024","journal-title":"Neuron"},{"key":"e_1_2_8_47_1","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 C\u2010C","year":"2013","journal-title":"Nat Rev Neurol"},{"key":"e_1_2_8_48_1","doi-asserted-by":"crossref","first-page":"5253","DOI":"10.1074\/jbc.M111.276162","article-title":"Small molecule structure correctors abolish detrimental effects of apolipoprotein E4 in cultured neurons","volume":"287","author":"Chen H\u2010K","year":"2012","journal-title":"J Biol Chem"},{"key":"e_1_2_8_49_1","doi-asserted-by":"crossref","first-page":"18700","DOI":"10.1073\/pnas.0508693102","article-title":"Apolipoprotein (apo) E4 enhances amyloid beta peptide production in cultured neuronal cells: apoE structure as a potential therapeutic target","volume":"102","author":"Ye S","year":"2005","journal-title":"Proc Natl Acad Sci USA"},{"key":"e_1_2_8_50_1","doi-asserted-by":"crossref","DOI":"10.3390\/molecules30040940","article-title":"Discovery of Isobavachin, a natural flavonoid, as an apolipoprotein E4 (ApoE4) structure corrector for Alzheimer's disease","volume":"30","author":"Patil SP","year":"2025","journal-title":"Molecules"},{"key":"e_1_2_8_51_1","doi-asserted-by":"crossref","first-page":"97","DOI":"10.2174\/1573409914666181008164209","article-title":"In silico identification of novel apolipoprotein E4 inhibitor for Alzheimer's disease therapy","volume":"15","author":"Bano S","year":"2019","journal-title":"Curr Comput Aided Drug Des"},{"key":"e_1_2_8_52_1","doi-asserted-by":"crossref","first-page":"179","DOI":"10.1016\/j.neuropharm.2016.04.032","article-title":"Quercetin stabilizes apolipoprotein E and reduces brain A\u03b2 levels in amyloid model mice","volume":"108","author":"Zhang X","year":"2016","journal-title":"Neuropharmacology"},{"key":"e_1_2_8_53_1","doi-asserted-by":"crossref","first-page":"1440","DOI":"10.1017\/S0007114508102434","article-title":"Effect of apoE genotype and dietary quercetin on blood lipids and TNF\u2010alpha levels in apoE3 and apoE4 targeted gene replacement mice","volume":"101","author":"Boesch\u2010Saadatmandi C","year":"2009","journal-title":"Br J Nutr"},{"key":"e_1_2_8_54_1","doi-asserted-by":"crossref","DOI":"10.1016\/j.ajpc.2026.101442","article-title":"The emerging role of CETP inhibition in the prevention of Alzheimer's disease","volume":"26","author":"Davidson MH","year":"2026","journal-title":"Am J Prev Cardiol"},{"key":"e_1_2_8_55_1","doi-asserted-by":"crossref","DOI":"10.1016\/j.tjpad.2025.100394","article-title":"Effect of obicetrapib, a potent cholesteryl ester transfer protein inhibitor, on p\u2010tau217 levels in patients with cardiovascular disease","volume":"13","author":"Davidson MH","year":"2026","journal-title":"J Prev Alzheimers Dis"},{"key":"e_1_2_8_56_1","doi-asserted-by":"crossref","first-page":"2613","DOI":"10.1021\/acs.biochem.6b00324","article-title":"ApoE: in vitro studies of a Small molecule effector","volume":"55","author":"Mondal T","year":"2016","journal-title":"Biochemistry"},{"key":"e_1_2_8_57_1","doi-asserted-by":"crossref","first-page":"1175","DOI":"10.1038\/s43587-021-00138-z","article-title":"Endophenotype\u2010based in silico network medicine discovery combined with insurance record data mining identifies sildenafil as a candidate drug for Alzheimer's disease","volume":"1","author":"Fang J","year":"2021","journal-title":"Nat Aging"},{"key":"e_1_2_8_58_1","doi-asserted-by":"crossref","first-page":"712","DOI":"10.1038\/s41586-025-09335-x","article-title":"Lithium deficiency and the onset of Alzheimer's disease","volume":"645","author":"Aron L","year":"2025","journal-title":"Nature"},{"key":"e_1_2_8_59_1","doi-asserted-by":"crossref","first-page":"2212","DOI":"10.1056\/NEJMe2403712","article-title":"Protection against Alzheimer's disease with APOE Christchurch variant \u2010 how?","volume":"390","author":"Hardy J","year":"2024","journal-title":"N Engl J Med"},{"key":"e_1_2_8_60_1","doi-asserted-by":"crossref","first-page":"63","DOI":"10.1186\/s13024-020-00413-4","article-title":"APOE2: protective mechanism and therapeutic implications for Alzheimer's disease","volume":"15","author":"Li Z","year":"2020","journal-title":"Mol Neurodegener"},{"key":"e_1_2_8_61_1","doi-asserted-by":"crossref","first-page":"661","DOI":"10.1016\/j.neuron.2025.10.040","article-title":"Protective ApoE variants support neuronal function by effluxing oxidized phospholipids","volume":"114","author":"Ralhan I","year":"2026","journal-title":"Neuron"},{"key":"e_1_2_8_62_1","doi-asserted-by":"crossref","DOI":"10.1126\/scitranslmed.3007000","article-title":"Gene transfer of human Apoe isoforms results in differential modulation of amyloid deposition and neurotoxicity in mouse brain","volume":"5","author":"Hudry E","year":"2013","journal-title":"Sci Transl Med"},{"key":"e_1_2_8_63_1","doi-asserted-by":"crossref","first-page":"24","DOI":"10.1089\/humc.2017.231","article-title":"AAVrh.10\u2010mediated APOE2 central nervous system gene therapy for APOE4\u2010associated Alzheimer's disease","volume":"29","author":"Rosenberg JB","year":"2018","journal-title":"Hum Gene Ther Clin Dev"},{"key":"e_1_2_8_64_1","doi-asserted-by":"crossref","first-page":"483","DOI":"10.1172\/JCI113096","article-title":"Apolipoprotein E2\u2010Christchurch (136 Arg\u2014Ser). New variant of human apolipoprotein E in a patient with type III hyperlipoproteinemia","volume":"80","author":"Wardell MR","year":"1987","journal-title":"J Clin Invest"},{"key":"e_1_2_8_65_1","doi-asserted-by":"crossref","first-page":"1680","DOI":"10.1038\/s41591-019-0611-3","article-title":"Resistance to autosomal dominant Alzheimer's disease in an APOE3 Christchurch homozygote: a case report","volume":"25","author":"Arboleda\u2010Velasquez JF","year":"2019","journal-title":"Nat Med"},{"key":"e_1_2_8_66_1","doi-asserted-by":"crossref","first-page":"2104","DOI":"10.1038\/s41593-023-01480-8","article-title":"The APOE\u2010R136S mutation protects against APOE4\u2010driven Tau pathology, neurodegeneration and neuroinflammation","volume":"26","author":"Nelson MR","year":"2023","journal-title":"Nat Neurosci"},{"key":"e_1_2_8_67_1","doi-asserted-by":"crossref","first-page":"1931","DOI":"10.1016\/j.immuni.2025.05.023","article-title":"The R136S mutation in the APOE3 gene confers resilience against tau pathology via inhibition of the cGAS\u2010STING\u2010IFN pathway","volume":"58","author":"Naguib S","year":"2025","journal-title":"Immunity"},{"key":"e_1_2_8_68_1","doi-asserted-by":"crossref","first-page":"819","DOI":"10.1002\/alz.13436","article-title":"APOE Christchurch\u2010mimetic therapeutic antibody reduces APOE\u2010mediated toxicity and tau phosphorylation","volume":"20","author":"Marino C","year":"2024","journal-title":"Alzheimers Dement"},{"key":"e_1_2_8_69_1","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\u2010induced tau seeding and spread","volume":"187","author":"Chen Y","year":"2024","journal-title":"Cell"},{"key":"e_1_2_8_70_1","doi-asserted-by":"crossref","DOI":"10.1016\/j.celrep.2024.114982","article-title":"Microglial APOE3 Christchurch protects neurons from tau pathology in a human iPSC\u2010based model of Alzheimer's disease","volume":"43","author":"Sun GG","year":"2024","journal-title":"Cell Rep"},{"key":"e_1_2_8_71_1","article-title":"Hepatic expression of APOE3 Christchurch mitigates APOE4\u2010related Alzheimer's disease pathologies in mice","author":"Tang J\u2010Y","year":"2026","journal-title":"Neuron"},{"key":"e_1_2_8_72_1","doi-asserted-by":"crossref","first-page":"1110","DOI":"10.1016\/j.neuron.2024.01.008","article-title":"APOE loss\u2010of\u2010function variants: compatible with longevity and associated with resistance to Alzheimer's disease pathology","volume":"112","author":"Chemparathy A","year":"2024","journal-title":"Neuron"},{"key":"e_1_2_8_73_1","doi-asserted-by":"crossref","first-page":"337","DOI":"10.1002\/humu.20288","article-title":"Apolipoprotein (APOE) gene is associated with progression of age\u2010related macular degeneration (AMD)","volume":"27","author":"Baird PN","year":"2006","journal-title":"Hum Mutat"},{"key":"e_1_2_8_74_1","doi-asserted-by":"crossref","DOI":"10.1186\/s13024-024-00747-3","article-title":"Whole\u2010genome sequencing analysis reveals new susceptibility loci and structural variants associated with progressive supranuclear palsy","volume":"19","author":"Wang H","year":"2024","journal-title":"Mol Neurodegener"},{"key":"e_1_2_8_75_1","doi-asserted-by":"crossref","first-page":"960","DOI":"10.1038\/s41431-025-01872-3","article-title":"A Spanish\u2010Portuguese GWAS of progressive supranuclear palsy reveals a novel risk locus in NFASC","volume":"33","author":"Garc\u00eda\u2010Gonz\u00e1lez P","year":"2025","journal-title":"Eur J Hum Genet"},{"key":"e_1_2_8_76_1","doi-asserted-by":"crossref","first-page":"1829","DOI":"10.1126\/science.1112766","article-title":"Suppression of aging in mice by the hormone klotho","volume":"309","author":"Kurosu H","year":"2005","journal-title":"Science"},{"key":"e_1_2_8_77_1","doi-asserted-by":"crossref","first-page":"45","DOI":"10.1038\/36285","article-title":"Mutation of the mouse klotho gene leads to a syndrome resembling ageing","volume":"390","author":"Kuro\u2010o M","year":"1997","journal-title":"Nature"},{"key":"e_1_2_8_78_1","doi-asserted-by":"crossref","first-page":"849","DOI":"10.1001\/jamaneurol.2020.0414","article-title":"Association of Klotho\u2010VS heterozygosity with risk of Alzheimer disease in individuals who carry APOE4","volume":"77","author":"Belloy ME","year":"2020","journal-title":"JAMA Neurol"},{"key":"e_1_2_8_79_1","doi-asserted-by":"crossref","first-page":"e1878","DOI":"10.1212\/WNL.0000000000007323","article-title":"KLOTHO heterozygosity attenuates APOE4\u2010related amyloid burden in preclinical AD","volume":"92","author":"Erickson CM","year":"2019","journal-title":"Neurology"},{"key":"e_1_2_8_80_1","doi-asserted-by":"crossref","DOI":"10.1073\/pnas.2416042122","article-title":"Impact of APOE, klotho, and sex on cognitive decline with aging","volume":"122","author":"Shibata K","year":"2025","journal-title":"Proc Natl Acad Sci USA"},{"key":"e_1_2_8_81_1","doi-asserted-by":"crossref","first-page":"337","DOI":"10.1038\/s41398-023-02632-x","article-title":"Relationship of klotho with cognition and dementia: results from the NHANES 2011\u20102014 and mendelian randomization study","volume":"13","author":"Wu Y","year":"2023","journal-title":"Transl Psychiatry"},{"key":"e_1_2_8_82_1","doi-asserted-by":"crossref","DOI":"10.3389\/fnagi.2023.1053390","article-title":"The relationship between serum klotho and cognitive performance in a nationally representative sample of US adults","volume":"15","author":"Linghui D","year":"2023","journal-title":"Front Aging Neurosci"},{"key":"e_1_2_8_83_1","doi-asserted-by":"crossref","first-page":"391","DOI":"10.1007\/s11682-016-9598-2","article-title":"Systemic klotho is associated with KLOTHO variation and predicts intrinsic cortical connectivity in healthy human aging","volume":"11","author":"Yokoyama JS","year":"2017","journal-title":"Brain Imaging Behav"},{"key":"e_1_2_8_84_1","doi-asserted-by":"crossref","first-page":"319","DOI":"10.1038\/nature09788","article-title":"Caspase signalling controls microglia activation and neurotoxicity","volume":"472","author":"Burguillos MA","year":"2011","journal-title":"Nature"},{"key":"e_1_2_8_85_1","doi-asserted-by":"crossref","first-page":"445","DOI":"10.1186\/s12864-016-2725-z","article-title":"A loss of function variant in CASP7 protects against Alzheimer's disease in homozygous APOE \u03b54 allele carriers","volume":"17","author":"Ayers KL","year":"2016","journal-title":"BMC Genomics"},{"key":"e_1_2_8_86_1","doi-asserted-by":"crossref","first-page":"42504","DOI":"10.18632\/oncotarget.6391","article-title":"Genome\u2010wide haplotype association study identify TNFRSF1A, CASP7, LRP1B, CDH1 and TG genes associated with Alzheimer's disease in Caribbean Hispanic individuals","volume":"6","author":"Shang Z","year":"2015","journal-title":"Oncotarget"},{"key":"e_1_2_8_87_1","doi-asserted-by":"crossref","first-page":"3861","DOI":"10.1242\/jcs.00059","article-title":"Fibronectin at a glance","volume":"115","author":"Pankov R","year":"2002","journal-title":"J Cell Sci"},{"key":"e_1_2_8_88_1","doi-asserted-by":"crossref","first-page":"70","DOI":"10.1007\/s00401-024-02721-1","article-title":"Rare genetic variation in fibronectin 1 (FN1) protects against APOE\u03b54 in Alzheimer's disease","volume":"147","author":"Bhattarai P","year":"2024","journal-title":"Acta Neuropathol"},{"key":"e_1_2_8_89_1","first-page":"231","article-title":"rs140926439 variant in the fibronectin FN1 gene lowers risk of Alzheimer disease in APOE\u03b54 carriers in the UK biobank cohort","volume":"39","author":"Lehrer S","year":"2025","journal-title":"Alzheimer Dis Assoc Disord"},{"key":"e_1_2_8_90_1","doi-asserted-by":"crossref","first-page":"464","DOI":"10.1126\/science.1059817","article-title":"HIFalpha targeted for VHL\u2010mediated destruction by proline hydroxylation: implications for O2 sensing","volume":"292","author":"Ivan M","year":"2001","journal-title":"Science"},{"key":"e_1_2_8_91_1","doi-asserted-by":"crossref","DOI":"10.1172\/JCI162480","article-title":"Von Hippel\u2010Lindau disease: insights into oxygen sensing, protein degradation, and cancer","volume":"132","author":"Kaelin WG","year":"2022","journal-title":"J Clin Invest"},{"key":"e_1_2_8_92_1","doi-asserted-by":"crossref","first-page":"1196","DOI":"10.1126\/science.1173507","article-title":"Proteasomal regulation of the hypoxic response modulates aging in C. Elegans","volume":"324","author":"Mehta R","year":"2009","journal-title":"Science"},{"key":"e_1_2_8_93_1","doi-asserted-by":"crossref","first-page":"610","DOI":"10.1007\/s13238-019-0621-4","article-title":"VHL\u20101 inactivation and mitochondrial antioxidants rescue C. Elegans dopaminergic neurodegeneration","volume":"10","author":"Chen S","year":"2019","journal-title":"Protein Cell"},{"key":"e_1_2_8_94_1","doi-asserted-by":"crossref","DOI":"10.1073\/pnas.2417515122","article-title":"Suppressing APOE4\u2010induced neural pathologies by targeting the VHL\u2010HIF axis","volume":"122","author":"Jiang WI","year":"2025","journal-title":"Proc Natl Acad Sci USA"},{"key":"e_1_2_8_95_1","doi-asserted-by":"crossref","first-page":"704","DOI":"10.1038\/s44319-025-00664-6","article-title":"Conserved lipid metabolic reprogramming confers hypoxic and aging resilience","volume":"27","author":"Jiang WI","year":"2026","journal-title":"EMBO Rep"},{"key":"e_1_2_8_96_1","doi-asserted-by":"crossref","first-page":"853","DOI":"10.1016\/j.cell.2025.12.020","article-title":"Peripheral cancer attenuates amyloid pathology in Alzheimer's disease via cystatin\u2010c activation of TREM2","volume":"189","author":"Li X","year":"2026","journal-title":"Cell"},{"key":"e_1_2_8_97_1","doi-asserted-by":"crossref","first-page":"97","DOI":"10.1016\/j.neuron.2013.07.043","article-title":"Christianson syndrome protein NHE6 modulates TrkB endosomal signaling required for neuronal circuit development","volume":"80","author":"Ouyang Q","year":"2013","journal-title":"Neuron"},{"key":"e_1_2_8_98_1","doi-asserted-by":"crossref","first-page":"E6640","DOI":"10.1073\/pnas.1801612115","article-title":"Amyloid clearance defect in ApoE4 astrocytes is reversed by epigenetic correction of endosomal pH","volume":"115","author":"Prasad H","year":"2018","journal-title":"Proc Natl Acad Sci USA"},{"key":"e_1_2_8_99_1","doi-asserted-by":"crossref","DOI":"10.7554\/eLife.40048","article-title":"Reversal of ApoE4\u2010induced recycling block as a novel prevention approach for Alzheimer's disease","volume":"7","author":"Xian X","year":"2018","journal-title":"elife"},{"key":"e_1_2_8_100_1","doi-asserted-by":"crossref","DOI":"10.7554\/eLife.72034","article-title":"NHE6 depletion corrects ApoE4\u2010mediated synaptic impairments and reduces amyloid plaque load","volume":"10","author":"Pohlkamp T","year":"2021","journal-title":"elife"},{"key":"e_1_2_8_101_1","doi-asserted-by":"crossref","first-page":"29","DOI":"10.1097\/WAD.0000000000000477","article-title":"Genetic variants and haplotypes of TOMM40, APOE, and APOC1 are related to the age of onset of late\u2010onset Alzheimer disease in a Colombian population","volume":"36","author":"Ortega\u2010Rojas J","year":"2022","journal-title":"Alzheimer Dis Assoc Disord"},{"key":"e_1_2_8_102_1","doi-asserted-by":"crossref","first-page":"1243","DOI":"10.1038\/s41591-023-02318-3","article-title":"Resilience to autosomal dominant Alzheimer's disease in a reelin\u2010COLBOS heterozygous man","volume":"29","author":"Lopera F","year":"2023","journal-title":"Nat Med"},{"key":"e_1_2_8_103_1","doi-asserted-by":"crossref","DOI":"10.1002\/glia.70192","article-title":"Alzheimer's protection by PLC\u03b32 compacts plaques, redistributes microglia, and protects synapses in AppNL \u2010G\u2010F mice","volume":"74","author":"Bevan RJ","year":"2026","journal-title":"Glia"},{"key":"e_1_2_8_104_1","doi-asserted-by":"crossref","first-page":"2632","DOI":"10.1002\/alz.13703","article-title":"Silencing Apoe with divalent\u2010siRNAs improves amyloid burden and activates immune response pathways in Alzheimer's disease","volume":"20","author":"Ferguson CM","year":"2024","journal-title":"Alzheimers Dement"},{"key":"e_1_2_8_105_1","doi-asserted-by":"crossref","first-page":"952","DOI":"10.1002\/ana.26043","article-title":"Apolipoprotein E4 reduction with antisense oligonucleotides decreases neurodegeneration in a tauopathy model","volume":"89","author":"Litvinchuk A","year":"2021","journal-title":"Ann Neurol"},{"key":"e_1_2_8_106_1","doi-asserted-by":"crossref","DOI":"10.1016\/j.ijbiomac.2026.151352","article-title":"CRISPR\u2010based correction of apolipoprotein E4 in Alzheimer's disease: therapeutic strategies and macromolecular delivery innovations","volume":"354","author":"Wang M","year":"2026","journal-title":"Int J Biol Macromol"},{"key":"e_1_2_8_107_1","doi-asserted-by":"crossref","first-page":"2461","DOI":"10.1038\/s41593-025-02094-y","article-title":"APOE4 to APOE2 allelic switching in mice improves Alzheimer's disease\u2010related metabolic signatures, neuropathology and cognition","volume":"28","author":"Golden LR","year":"2025","journal-title":"Nat Neurosci"},{"key":"e_1_2_8_108_1","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\u2010derived brain cell types","volume":"98","author":"Lin Y\u2010T","year":"2018","journal-title":"Neuron"},{"key":"e_1_2_8_109_1","doi-asserted-by":"crossref","first-page":"73","DOI":"10.1016\/j.omtm.2022.09.002","article-title":"Selection of rAAV vectors that cross the human blood\u2010brain barrier and target the central nervous system using a transwell model","volume":"27","author":"Song R","year":"2022","journal-title":"Mol Ther Methods Clin Dev"},{"key":"e_1_2_8_110_1","doi-asserted-by":"crossref","first-page":"78","DOI":"10.1038\/s41392-024-01780-w","article-title":"Adeno\u2010associated virus as a delivery vector for gene therapy of human diseases","volume":"9","author":"Wang J\u2010H","year":"2024","journal-title":"Signal Transduct Target Ther"},{"key":"e_1_2_8_111_1","doi-asserted-by":"crossref","first-page":"221","DOI":"10.1016\/j.jconrel.2024.11.074","article-title":"Lipid nanoparticles and transcranial focused ultrasound enhance the delivery of SOD1 antisense oligonucleotides to the murine brain for ALS therapy","volume":"378","author":"Ediriweera GR","year":"2025","journal-title":"J Control Release"},{"key":"e_1_2_8_112_1","doi-asserted-by":"crossref","first-page":"362","DOI":"10.1038\/s41573-021-00139-y","article-title":"Strategies for delivering therapeutics across the blood\u2010brain barrier","volume":"20","author":"Terstappen GC","year":"2021","journal-title":"Nat Rev Drug Discov"},{"key":"e_1_2_8_113_1","doi-asserted-by":"crossref","DOI":"10.1126\/scitranslmed.aay1359","article-title":"Brain delivery of therapeutic proteins using an fc fragment blood\u2010brain barrier transport vehicle in mice and monkeys","volume":"12","author":"Kariolis MS","year":"2020","journal-title":"Sci Transl Med"},{"key":"e_1_2_8_114_1","doi-asserted-by":"crossref","DOI":"10.1016\/j.celbio.2025.100344","article-title":"Engineered exosomes as precision tools for brain\u2010targeted drug delivery and treatment of central nervous system diseases","volume":"2","author":"Jin Y","year":"2026","journal-title":"Cell Biomater"},{"key":"e_1_2_8_115_1","doi-asserted-by":"crossref","unstructured":"TeterB CampagnaJ ZhuC McCauleyGE SpilmanP KohnDB&JohnV(2024)Successful gene editing of apolipoprotein E4 to E3 in brain of Alzheimer model mice after a single IV dose of synthetic exosome\u2010delivered CRISPR. 2024.04.23.590784.","DOI":"10.1101\/2024.04.23.590784"},{"key":"e_1_2_8_116_1","doi-asserted-by":"crossref","first-page":"739","DOI":"10.1007\/s00109-016-1427-y","article-title":"Apolipoprotein E: from cardiovascular disease to neurodegenerative disorders","volume":"94","author":"Mahley RW","year":"2016","journal-title":"J Mol Med (Berl)"},{"key":"e_1_2_8_117_1","doi-asserted-by":"crossref","first-page":"902","DOI":"10.1002\/1873-3468.14858","article-title":"Generation of novel anti\u2010apoE monoclonal antibodies that selectively recognize apoE isoforms","volume":"598","author":"Ohgita T","year":"2024","journal-title":"FEBS Lett"},{"key":"e_1_2_8_118_1","doi-asserted-by":"crossref","first-page":"291","DOI":"10.1001\/jamaneurol.2021.5205","article-title":"Amyloid\u2010related imaging abnormalities and \u03b2\u2010amyloid\u2010targeting antibodies: a systematic review","volume":"79","author":"Filippi M","year":"2022","journal-title":"JAMA Neurol"},{"key":"e_1_2_8_119_1","doi-asserted-by":"crossref","first-page":"918","DOI":"10.2174\/1567205013666160404120817","article-title":"An anti\u2010apoE4 specific monoclonal antibody counteracts the pathological effects of apoE4 in vivo","volume":"13","author":"Luz I","year":"2016","journal-title":"Curr Alzheimer Res"},{"key":"e_1_2_8_120_1","doi-asserted-by":"crossref","first-page":"2149","DOI":"10.1084\/jem.20121274","article-title":"Anti\u2010apoE immunotherapy inhibits amyloid accumulation in a transgenic mouse model of a\u03b2 amyloidosis","volume":"209","author":"Kim J","year":"2012","journal-title":"J Exp Med"},{"key":"e_1_2_8_121_1","doi-asserted-by":"crossref","first-page":"2144","DOI":"10.1172\/JCI96429","article-title":"Targeting of nonlipidated, aggregated apoE with antibodies inhibits amyloid accumulation","volume":"128","author":"Liao F","year":"2018","journal-title":"J Clin Invest"},{"key":"e_1_2_8_122_1","doi-asserted-by":"crossref","unstructured":"ParkSH GomesG\u2010N BeyerBA&LevineZA(2026)Inhibition of ApoE4 endocytosis with LDLR\u2010LA peptides. 2026.05.20.726622.","DOI":"10.64898\/2026.05.20.726622"},{"key":"e_1_2_8_123_1","doi-asserted-by":"crossref","first-page":"275","DOI":"10.1038\/s43587-023-00368-3","article-title":"Neuronal APOE4 removal protects against tau\u2010mediated gliosis, neurodegeneration and myelin deficits","volume":"3","author":"Koutsodendris N","year":"2023","journal-title":"Nat Aging"},{"key":"e_1_2_8_124_1","doi-asserted-by":"crossref","first-page":"18787","DOI":"10.1073\/pnas.0604011103","article-title":"Blocking the apolipoprotein E\/amyloid\u2010beta interaction as a potential therapeutic approach for Alzheimer's disease","volume":"103","author":"Sadowski MJ","year":"2006","journal-title":"Proc Natl Acad Sci USA"},{"key":"e_1_2_8_125_1","doi-asserted-by":"crossref","first-page":"779","DOI":"10.2174\/1570159X01666160930121647","article-title":"Recombinant antibody fragments for neurodegenerative diseases","volume":"15","author":"Manoutcharian K","year":"2017","journal-title":"Curr Neuropharmacol"},{"key":"e_1_2_8_126_1","doi-asserted-by":"crossref","first-page":"3","DOI":"10.1007\/978-1-61779-968-6_1","article-title":"From whole monoclonal antibodies to single domain antibodies: think small","volume":"911","author":"Teillaud J\u2010L","year":"2012","journal-title":"Methods Mol Biol"},{"key":"e_1_2_8_127_1","doi-asserted-by":"crossref","DOI":"10.3390\/cells15050479","article-title":"A nanobody\u2010based toolbox to probe ApoE4 in the secretory pathway and cytosol","volume":"15","author":"Vandevelde L","year":"2026","journal-title":"Cells"},{"key":"e_1_2_8_128_1","doi-asserted-by":"crossref","DOI":"10.1016\/j.tjpad.2025.100214","article-title":"Bispecific brain\u2010penetrant antibodies for treatment of Alzheimer's disease","volume":"12","author":"Sehlin D","year":"2025","journal-title":"J Prev Alzheimers Dis"},{"key":"e_1_2_8_129_1","doi-asserted-by":"crossref","DOI":"10.3390\/ijms26136271","article-title":"Recent advances in antibody therapy for Alzheimer's disease: focus on bispecific antibodies","volume":"26","author":"Yang H\u2010M","year":"2025","journal-title":"Int J Mol Sci"},{"key":"e_1_2_8_130_1","doi-asserted-by":"crossref","first-page":"47812","DOI":"10.1074\/jbc.M307002200","article-title":"Intradiabodies, bispecific, tetravalent antibodies for the simultaneous functional knockout of two cell surface receptors","volume":"278","author":"Jendreyko N","year":"2003","journal-title":"J Biol Chem"},{"key":"e_1_2_8_131_1","doi-asserted-by":"crossref","DOI":"10.1016\/j.fct.2019.110872","article-title":"APOE genotype and postnatal chlorpyrifos exposure modulate gut microbiota and cerebral short\u2010chain fatty acids in preweaning mice","volume":"135","author":"Guardia\u2010Escote L","year":"2020","journal-title":"Food Chem Toxicol"},{"key":"e_1_2_8_132_1","doi-asserted-by":"crossref","first-page":"122","DOI":"10.1186\/s13195-025-01769-9","article-title":"Compositional and functional gut microbiota alterations in mild cognitive impairment: links to Alzheimer's disease pathology","volume":"17","author":"Fan K\u2010C","year":"2025","journal-title":"Alzheimer's Res Ther"}],"container-title":["The FEBS Journal"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/febs.onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/febs.70759","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/febs.onlinelibrary.wiley.com\/doi\/full-xml\/10.1111\/febs.70759","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/febs.onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/febs.70759","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,10,5]],"date-time":"2026-10-05T13:14:56Z","timestamp":1791206096000},"score":1,"resource":{"primary":{"URL":"https:\/\/febs.onlinelibrary.wiley.com\/doi\/10.1111\/febs.70759"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,10,5]]},"references-count":131,"alternative-id":["10.1111\/febs.70759"],"URL":"https:\/\/doi.org\/10.1111\/febs.70759","archive":["Portico"],"relation":{},"ISSN":["1742-464X","1742-4658"],"issn-type":[{"value":"1742-464X","type":"print"},{"value":"1742-4658","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,10,5]]},"assertion":[{"value":"2026-05-11","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-09-25","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-10-05","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"febs.70759"}}