{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,24]],"date-time":"2026-09-24T05:14:51Z","timestamp":1790226891188,"version":"4.1.0"},"reference-count":350,"publisher":"Elsevier BV","issue":"16","license":[{"start":{"date-parts":[[2026,8,1]],"date-time":"2026-08-01T00:00:00Z","timestamp":1785542400000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/tdm\/userlicense\/1.0\/"},{"start":{"date-parts":[[2026,8,1]],"date-time":"2026-08-01T00:00:00Z","timestamp":1785542400000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/legal\/tdmrep-license"},{"start":{"date-parts":[[2026,4,18]],"date-time":"2026-04-18T00:00:00Z","timestamp":1776470400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000001","name":"National Science Foundation","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100000001","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000049","name":"National Institute on Aging","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100000049","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["cell.com","elsevier.com","sciencedirect.com"],"crossmark-restriction":true},"short-container-title":["Neuron"],"published-print":{"date-parts":[[2026,8]]},"DOI":"10.1016\/j.neuron.2026.04.024","type":"journal-article","created":{"date-parts":[[2026,5,14]],"date-time":"2026-05-14T15:12:40Z","timestamp":1778771560000},"page":"2929-2956","update-policy":"https:\/\/doi.org\/10.1016\/elsevier_cm_policy","source":"Crossref","is-referenced-by-count":2,"title":["Cell-type-specific APOE4 cascade across the Alzheimer\u2019s disease continuum"],"prefix":"10.1016","volume":"114","author":[{"given":"David","family":"Shostak","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zherui","family":"Liang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5871-4589","authenticated-orcid":false,"given":"Yadong","family":"Huang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"78","reference":[{"key":"10.1016\/j.neuron.2026.04.024_bib1","doi-asserted-by":"crossref","first-page":"312","DOI":"10.1016\/j.cell.2019.09.001","article-title":"Alzheimer disease: an update on pathobiology and treatment strategies","volume":"179","author":"Long","year":"2019","journal-title":"Cell"},{"key":"10.1016\/j.neuron.2026.04.024_bib2","doi-asserted-by":"crossref","first-page":"1204","DOI":"10.1016\/j.cell.2012.02.040","article-title":"Alzheimer mechanisms and therapeutic strategies","volume":"148","author":"Huang","year":"2012","journal-title":"Cell"},{"key":"10.1016\/j.neuron.2026.04.024_bib3","doi-asserted-by":"crossref","first-page":"401","DOI":"10.14283\/jpad.2023.54","article-title":"Neuroinflammation biomarkers in the AT(N) framework across the Alzheimer\u2019s disease continuum","volume":"10","author":"Bieger","year":"2023","journal-title":"J. Prev. Alzheimers Dis."},{"key":"10.1016\/j.neuron.2026.04.024_bib4","doi-asserted-by":"crossref","first-page":"580","DOI":"10.1038\/s41582-021-00520-w","article-title":"Developing the ATX(N) classification for use across the Alzheimer disease continuum","volume":"17","author":"Hampel","year":"2021","journal-title":"Nat. Rev. Neurol."},{"key":"10.1016\/j.neuron.2026.04.024_bib5","doi-asserted-by":"crossref","first-page":"7120","DOI":"10.1007\/s00415-024-12674-w","article-title":"Association between blood-based protein biomarkers and brain MRI in the Alzheimer\u2019s disease continuum: a systematic review","volume":"271","author":"Mitolo","year":"2024","journal-title":"J. Neurol."},{"key":"10.1016\/j.neuron.2026.04.024_bib6","doi-asserted-by":"crossref","first-page":"280","DOI":"10.1016\/j.jalz.2011.03.003","article-title":"Toward defining the preclinical stages of Alzheimer\u2019s disease: Recommendations from the National Institute on Aging-Alzheimer\u2019s Association workgroups on diagnostic guidelines for Alzheimer\u2019s disease","volume":"7","author":"Sperling","year":"2011","journal-title":"Alzheimers. Dement."},{"key":"10.1016\/j.neuron.2026.04.024_bib7","doi-asserted-by":"crossref","first-page":"351","DOI":"10.1001\/archneurol.2011.31","article-title":"Cognitive decline in prodromal Alzheimer disease and mild cognitive impairment","volume":"68","author":"Wilson","year":"2011","journal-title":"Arch. Neurol."},{"key":"10.1016\/j.neuron.2026.04.024_bib8","doi-asserted-by":"crossref","first-page":"658","DOI":"10.1002\/alz.12694","article-title":"Global estimates on the number of persons across the Alzheimer\u2019s disease continuum","volume":"19","author":"Gustavsson","year":"2023","journal-title":"Alzheimers. Dement."},{"key":"10.1016\/j.neuron.2026.04.024_bib9","doi-asserted-by":"crossref","DOI":"10.1186\/s13195-017-0283-5","article-title":"On the path to 2025: understanding the Alzheimer\u2019s disease continuum","volume":"9","author":"Aisen","year":"2017","journal-title":"Alzheimers Res. Ther."},{"key":"10.1016\/j.neuron.2026.04.024_bib10","doi-asserted-by":"crossref","DOI":"10.1212\/WNL.0000000000011883","article-title":"Association of APOE genotype with heterogeneity of cognitive decline rate in Alzheimer Disease","volume":"96","author":"Qian","year":"2021","journal-title":"Neurology"},{"key":"10.1016\/j.neuron.2026.04.024_bib11","doi-asserted-by":"crossref","first-page":"888","DOI":"10.1016\/j.jalz.2019.04.001","article-title":"Duration of preclinical, prodromal, and dementia stages of Alzheimer\u2019s disease in relation to age, sex, and APOE genotype","volume":"15","author":"Vermunt","year":"2019","journal-title":"Alzheimers. Dement."},{"key":"10.1016\/j.neuron.2026.04.024_bib12","doi-asserted-by":"crossref","first-page":"1842","DOI":"10.1212\/01.wnl.0000304038.37421.cc","article-title":"APOE \u03b54 allele predicts faster cognitive decline in mild Alzheimer\u2019s disease","volume":"70","author":"Cosentino","year":"2008","journal-title":"Neurology"},{"key":"10.1016\/j.neuron.2026.04.024_bib13","doi-asserted-by":"crossref","first-page":"622","DOI":"10.1126\/science.3283935","article-title":"Apolipoprotein E: cholesterol transport protein with expanding role in cell biology","volume":"240","author":"Mahley","year":"1988","journal-title":"Science"},{"key":"10.1016\/j.neuron.2026.04.024_bib14","doi-asserted-by":"crossref","first-page":"3","DOI":"10.1016\/j.nbd.2014.08.025","article-title":"Apolipoprotein E: Structure and function in lipid metabolism, neurobiology, and Alzheimer\u2019s diseases","volume":"72","author":"Huang","year":"2014","journal-title":"Neurobiol. Dis."},{"key":"10.1016\/j.neuron.2026.04.024_bib15","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1159\/000334607","article-title":"Prevalence of apolipoprotein E4 genotype and homozygotes (APOE e4\/4) among patients diagnosed with Alzheimer\u2019s disease: a systematic review and meta-analysis","volume":"38","author":"Ward","year":"2011","journal-title":"Neuroepidemiology"},{"key":"10.1016\/j.neuron.2026.04.024_bib16","doi-asserted-by":"crossref","first-page":"91","DOI":"10.1038\/s41583-023-00776-9","article-title":"Cell type-specific roles of APOE4 in Alzheimer disease","volume":"25","author":"Blumenfeld","year":"2024","journal-title":"Nat. Rev. Neurosci."},{"key":"10.1016\/j.neuron.2026.04.024_bib17","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\u2019s disease in late onset families","volume":"261","author":"Corder","year":"1993","journal-title":"Science"},{"key":"10.1016\/j.neuron.2026.04.024_bib18","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-analysis","volume":"278","author":"Farrer","year":"1997","journal-title":"JAMA"},{"key":"10.1016\/j.neuron.2026.04.024_bib19","doi-asserted-by":"crossref","DOI":"10.1186\/s41021-025-00332-0","article-title":"Genetics and environmental determinants of Alzheimer\u2019s disease and related dementias in older Africans: a narrative review","volume":"47","author":"Olajide","year":"2025","journal-title":"Genes Environ."},{"key":"10.1016\/j.neuron.2026.04.024_bib20","doi-asserted-by":"crossref","DOI":"10.1038\/s41467-026-68808-3","article-title":"A common 19 bp APOE enhancer deletion is protective against Alzheimer\u2019s disease in African Americans","volume":"17","author":"Brutman","year":"2026","journal-title":"Nat. Commun."},{"key":"10.1016\/j.neuron.2026.04.024_bib21","doi-asserted-by":"crossref","first-page":"1284","DOI":"10.1001\/jamaneurol.2023.3599","article-title":"APOE Genotype and Alzheimer Disease Risk Across Age, Sex, and Population Ancestry","volume":"80","author":"Belloy","year":"2023","journal-title":"JAMA Neurol."},{"key":"10.1016\/j.neuron.2026.04.024_bib22","doi-asserted-by":"crossref","first-page":"405","DOI":"10.1146\/annurev.biochem.71.110601.135342","article-title":"Lipoprotein receptors in the nervous system","volume":"71","author":"Herz","year":"2002","journal-title":"Annu. Rev. Biochem."},{"key":"10.1016\/j.neuron.2026.04.024_bib23","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","year":"2019","journal-title":"Nat. Rev. Neurol."},{"key":"10.1016\/j.neuron.2026.04.024_bib24","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"},{"key":"10.1016\/j.neuron.2026.04.024_bib25","doi-asserted-by":"crossref","first-page":"871","DOI":"10.1016\/j.neuron.2012.11.020","article-title":"Apolipoprotein E sets the stage: response to injury triggers neuropathology","volume":"76","author":"Mahley","year":"2012","journal-title":"Neuron"},{"key":"10.1016\/j.neuron.2026.04.024_bib26","doi-asserted-by":"crossref","first-page":"4985","DOI":"10.1523\/JNEUROSCI.5476-05.2006","article-title":"Profile and regulation of apolipoprotein E (ApoE) expression in the CNS in mice with targeting of green fluorescent protein gene to the ApoE locus","volume":"26","author":"Xu","year":"2006","journal-title":"J. Neurosci."},{"key":"10.1016\/j.neuron.2026.04.024_bib27","doi-asserted-by":"crossref","first-page":"1452","DOI":"10.1523\/JNEUROSCI.3253-07.2008","article-title":"Intron-3 retention\/splicing controls neuronal expression of apolipoprotein E in the CNS","volume":"28","author":"Xu","year":"2008","journal-title":"J. Neurosci."},{"key":"10.1016\/j.neuron.2026.04.024_bib28","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"},{"key":"10.1016\/j.neuron.2026.04.024_bib29","doi-asserted-by":"crossref","first-page":"1478","DOI":"10.1002\/glia.23974","article-title":"Expression and secretion of apoE isoforms in astrocytes and microglia during inflammation","volume":"69","author":"Lanfranco","year":"2021","journal-title":"Glia"},{"key":"10.1016\/j.neuron.2026.04.024_bib30","doi-asserted-by":"crossref","first-page":"3862","DOI":"10.1074\/jbc.M309475200","article-title":"Astroglial regulation of apolipoprotein E expression in neuronal cells: implications for Alzheimer\u2019s disease","volume":"279","author":"Harris","year":"2004","journal-title":"J. Biol. Chem."},{"key":"10.1016\/j.neuron.2026.04.024_bib31","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","year":"2024","journal-title":"Nat. Rev. Neurol."},{"key":"10.1016\/j.neuron.2026.04.024_bib32","doi-asserted-by":"crossref","first-page":"13","DOI":"10.1006\/exnr.1994.1108","article-title":"Apolipoprotein E is present in hippocampal neurons without neurofibrillary tangles in Alzheimer\u2019s disease and in age-matched controls","volume":"128","author":"Han","year":"1994","journal-title":"Exp. Neurol."},{"key":"10.1016\/j.neuron.2026.04.024_bib33","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\u2019s disease","volume":"24","author":"Zalocusky","year":"2021","journal-title":"Nat. Neurosci."},{"key":"10.1016\/j.neuron.2026.04.024_bib34","doi-asserted-by":"crossref","DOI":"10.1038\/s41467-023-37437-5","article-title":"Single-nucleus RNA-sequencing of autosomal dominant Alzheimer disease and risk variant carriers","volume":"14","author":"Brase","year":"2023","journal-title":"Nat. Commun."},{"key":"10.1016\/j.neuron.2026.04.024_bib35","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","year":"2014","journal-title":"J. Neurosci."},{"key":"10.1016\/j.neuron.2026.04.024_bib36","doi-asserted-by":"crossref","first-page":"726","DOI":"10.1002\/ana.25455","article-title":"Neuronal apolipoprotein E4 increases cell death and phosphorylated tau release in Alzheimer disease","volume":"85","author":"Wadhwani","year":"2019","journal-title":"Ann. Neurol."},{"key":"10.1016\/j.neuron.2026.04.024_bib37","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-derived neurons is ameliorated by a small-molecule structure corrector","volume":"24","author":"Wang","year":"2018","journal-title":"Nat. Med."},{"key":"10.1016\/j.neuron.2026.04.024_bib38","doi-asserted-by":"crossref","first-page":"271","DOI":"10.1016\/S1474-4422(19)30368-0","article-title":"The characterisation of subjective cognitive decline","volume":"19","author":"Jessen","year":"2020","journal-title":"Lancet Neurol."},{"key":"10.1016\/j.neuron.2026.04.024_bib39","doi-asserted-by":"crossref","first-page":"170","DOI":"10.1590\/S1980-5764-2016DN1003002","article-title":"Subjective cognitive decline: The first clinical manifestation of Alzheimer\u2019s disease?","volume":"10","author":"Studart","year":"2016","journal-title":"Dement. Neuropsychol."},{"key":"10.1016\/j.neuron.2026.04.024_bib40","doi-asserted-by":"crossref","first-page":"1284","DOI":"10.1038\/s41591-024-02931-w","article-title":"APOE4 homozygosity represents a distinct genetic form of Alzheimer\u2019s disease","volume":"30","author":"Fortea","year":"2024","journal-title":"Nat. Med."},{"key":"10.1016\/j.neuron.2026.04.024_bib41","doi-asserted-by":"crossref","first-page":"322","DOI":"10.1176\/appi.neuropsych.14100268","article-title":"APOE \u03b54 genotype and the risk for subjective cognitive impairment in elderly persons","volume":"27","author":"Krell-Roesch","year":"2015","journal-title":"J. Neuropsychiatry Clin. Neurosci."},{"key":"10.1016\/j.neuron.2026.04.024_bib42","doi-asserted-by":"crossref","first-page":"2556","DOI":"10.1038\/s41591-025-03834-0","article-title":"The Global Neurodegeneration Proteomics Consortium: biomarker and drug target discovery for common neurodegenerative diseases and aging","volume":"31","author":"Imam","year":"2025","journal-title":"Nat. Med."},{"key":"10.1016\/j.neuron.2026.04.024_bib43","article-title":"Proteomic signatures of the APOE \u03b54 and APOE \u03b52 genetic variants and Alzheimer\u2019s disease","author":"Lu","year":"2025","journal-title":"medRxiv"},{"key":"10.1016\/j.neuron.2026.04.024_bib44","doi-asserted-by":"crossref","first-page":"1898","DOI":"10.1016\/j.neuron.2023.03.024","article-title":"Differential and substrate-specific inhibition of \u03b3-secretase by the C-terminal region of ApoE2, ApoE3, and ApoE4","volume":"111","author":"Hou","year":"2023","journal-title":"Neuron"},{"key":"10.1016\/j.neuron.2026.04.024_bib45","doi-asserted-by":"crossref","first-page":"4365","DOI":"10.1016\/j.cell.2023.08.039","article-title":"Single-cell atlas reveals correlates of high cognitive function, dementia, and resilience to Alzheimer\u2019s disease pathology","volume":"186","author":"Mathys","year":"2023","journal-title":"Cell"},{"key":"10.1016\/j.neuron.2026.04.024_bib46","doi-asserted-by":"crossref","first-page":"634","DOI":"10.1016\/j.stem.2009.10.015","article-title":"GABAergic interneuron dysfunction impairs hippocampal neurogenesis in adult apolipoprotein E4 knockin mice","volume":"5","author":"Li","year":"2009","journal-title":"Cell Stem Cell"},{"key":"10.1016\/j.neuron.2026.04.024_bib47","doi-asserted-by":"crossref","DOI":"10.1371\/journal.pone.0053569","article-title":"Apolipoprotein E4 causes age- and sex-dependent impairments of hilar GABAergic interneurons and learning and memory deficits in mice","volume":"7","author":"Leung","year":"2012","journal-title":"PLoS One"},{"key":"10.1016\/j.neuron.2026.04.024_bib48","doi-asserted-by":"crossref","first-page":"13707","DOI":"10.1523\/JNEUROSCI.4040-10.2010","article-title":"Apolipoprotein E4 causes age- and tau-dependent impairment of GABAergic interneurons, leading to learning and memory deficits in mice","volume":"30","author":"Andrews-Zwilling","year":"2010","journal-title":"J. Neurosci."},{"key":"10.1016\/j.neuron.2026.04.024_bib49","doi-asserted-by":"crossref","first-page":"2316","DOI":"10.1523\/JNEUROSCI.3815-15.2016","article-title":"Enhancing GABA signaling during middle adulthood prevents age-dependent GABAergic interneuron decline and learning and memory deficits in ApoE4 mice","volume":"36","author":"Tong","year":"2016","journal-title":"J. Neurosci."},{"key":"10.1016\/j.neuron.2026.04.024_bib50","doi-asserted-by":"crossref","first-page":"2366","DOI":"10.1038\/s41593-024-01774-5","article-title":"Integrated multimodal cell atlas of Alzheimer\u2019s disease","volume":"27","author":"Gabitto","year":"2024","journal-title":"Nat. Neurosci."},{"key":"10.1016\/j.neuron.2026.04.024_bib51","doi-asserted-by":"crossref","first-page":"450","DOI":"10.1056\/NEJM200008173430701","article-title":"Patterns of brain activation in people at risk for Alzheimer\u2019s disease","volume":"343","author":"Bookheimer","year":"2000","journal-title":"N. Engl. J. Med."},{"key":"10.1016\/j.neuron.2026.04.024_bib52","doi-asserted-by":"crossref","first-page":"7209","DOI":"10.1073\/pnas.0811879106","article-title":"Distinct patterns of brain activity in young carriers of the APOE-\u03b54 allele","volume":"106","author":"Filippini","year":"2009","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"10.1016\/j.neuron.2026.04.024_bib53","doi-asserted-by":"crossref","first-page":"467","DOI":"10.1016\/j.neuron.2012.03.023","article-title":"Reduction of hippocampal hyperactivity improves cognition in amnestic mild cognitive impairment","volume":"74","author":"Bakker","year":"2012","journal-title":"Neuron"},{"key":"10.1016\/j.neuron.2026.04.024_bib54","doi-asserted-by":"crossref","DOI":"10.1186\/s13024-019-0324-6","article-title":"Apolipoprotein E4, inhibitory network dysfunction, and Alzheimer\u2019s disease","volume":"14","author":"Najm","year":"2019","journal-title":"Mol. Neurodegener."},{"key":"10.1016\/j.neuron.2026.04.024_bib55","doi-asserted-by":"crossref","DOI":"10.1038\/s41467-017-01444-0","article-title":"Neuronal hyperactivity due to loss of inhibitory tone in APOE4 mice lacking Alzheimer\u2019s disease-like pathology","volume":"8","author":"Nuriel","year":"2017","journal-title":"Nat. Commun."},{"key":"10.1016\/j.neuron.2026.04.024_bib56","doi-asserted-by":"crossref","first-page":"740","DOI":"10.1016\/j.neuron.2016.04.009","article-title":"Apolipoprotein E4 causes age-dependent disruption of slow gamma oscillations during hippocampal sharp-wave ripples","volume":"90","author":"Gillespie","year":"2016","journal-title":"Neuron"},{"key":"10.1016\/j.neuron.2026.04.024_bib57","doi-asserted-by":"crossref","DOI":"10.1038\/s43587-026-01096-0","article-title":"Neuronal APOE4-induced early hippocampal network hyperexcitability in Alzheimer's disease pathogenesis","author":"Tabuena","year":"2026","journal-title":"Nat. Aging"},{"key":"10.1016\/j.neuron.2026.04.024_bib58","doi-asserted-by":"crossref","first-page":"2123","DOI":"10.1016\/j.celrep.2019.10.056","article-title":"Early hippocampal sharp-wave ripple deficits predict later learning and memory impairments in an Alzheimer\u2019s disease mouse model","volume":"29","author":"Jones","year":"2019","journal-title":"Cell Rep."},{"key":"10.1016\/j.neuron.2026.04.024_bib59","article-title":"Tri-AD: Hippocampal cell-type-specific responses to age, sex and APOE genotype","author":"Li","year":"2025","journal-title":"bioRxiv"},{"key":"10.1016\/j.neuron.2026.04.024_bib60","doi-asserted-by":"crossref","first-page":"1181","DOI":"10.1038\/npp.2014.302","article-title":"Disrupted functional and structural networks in cognitively normal elderly subjects with the APOE \u03f54 allele","volume":"40","author":"Chen","year":"2015","journal-title":"Neuropsychopharmacology"},{"key":"10.1016\/j.neuron.2026.04.024_bib61","doi-asserted-by":"crossref","first-page":"8802","DOI":"10.1002\/alz.14327","article-title":"SV2A PET shows hippocampal synaptic loss in cognitively unimpaired APOE \u03b54\/\u03b54 homozygotes","volume":"20","author":"Snellman","year":"2024","journal-title":"Alzheimers Dement."},{"key":"10.1016\/j.neuron.2026.04.024_bib62","doi-asserted-by":"crossref","first-page":"277","DOI":"10.1016\/S0002-9440(10)64538-5","article-title":"Endocytic pathway abnormalities precede amyloid \u03b2 deposition in sporadic Alzheimer\u2019s disease and Down syndrome: differential effects of APOE genotype and presenilin mutations","volume":"157","author":"Cataldo","year":"2000","journal-title":"Am. J. Pathol."},{"key":"10.1016\/j.neuron.2026.04.024_bib63","doi-asserted-by":"crossref","first-page":"40","DOI":"10.1212\/WNL.0000000000001702","article-title":"Altered lysosomal proteins in neural-derived plasma exosomes in preclinical Alzheimer disease","volume":"85","author":"Goetzl","year":"2015","journal-title":"Neurology"},{"key":"10.1016\/j.neuron.2026.04.024_bib64","doi-asserted-by":"crossref","first-page":"320","DOI":"10.1001\/2013.jamaneurol.286","article-title":"Posterior cingulate glucose metabolism, hippocampal glucose metabolism, and hippocampal volume in cognitively normal, late-middle-aged persons at 3 levels of genetic risk for Alzheimer disease","volume":"70","author":"Protas","year":"2013","journal-title":"JAMA Neurol."},{"key":"10.1016\/j.neuron.2026.04.024_bib65","doi-asserted-by":"crossref","first-page":"8299","DOI":"10.1073\/pnas.0500579102","article-title":"Correlations between apolipoprotein E \u03b54 gene dose and brain-imaging measurements of regional hypometabolism","volume":"102","author":"Reiman","year":"2005","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"10.1016\/j.neuron.2026.04.024_bib66","doi-asserted-by":"crossref","first-page":"942","DOI":"10.1001\/jama.1995.03520360056039","article-title":"Apolipoprotein E Type 4 Allele and Cerebral Glucose Metabolism in Relatives at Risk for Familial Alzheimer Disease","volume":"273","author":"Small","year":"1995","journal-title":"JAMA"},{"key":"10.1016\/j.neuron.2026.04.024_bib67","doi-asserted-by":"crossref","first-page":"3334","DOI":"10.1073\/pnas.061509598","article-title":"Declining brain activity in cognitively normal apolipoprotein E \u03f54 heterozygotes: A foundation for using positron emission tomography to efficiently test treatments to prevent Alzheimer\u2019s disease","volume":"98","author":"Reiman","year":"2001","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"10.1016\/j.neuron.2026.04.024_bib68","doi-asserted-by":"crossref","first-page":"4695","DOI":"10.1038\/s41467-024-49028-z","article-title":"Co-aggregation with apolipoprotein E modulates the function of Amyloid-\u03b2 in Alzheimer\u2019s disease","volume":"15","author":"Xia","year":"2024","journal-title":"Nat. Commun."},{"key":"10.1016\/j.neuron.2026.04.024_bib69","doi-asserted-by":"crossref","first-page":"1024","DOI":"10.1016\/j.neuron.2017.11.013","article-title":"ApoE4 accelerates early seeding of amyloid pathology","volume":"96","author":"Liu","year":"2017","journal-title":"Neuron"},{"key":"10.1016\/j.neuron.2026.04.024_bib70","doi-asserted-by":"crossref","first-page":"1621","DOI":"10.1016\/j.ajpath.2019.04.010","article-title":"Apolipoprotein E\/amyloid-\u03b2 complex accumulates in Alzheimer disease cortical synapses via apolipoprotein E receptors and is enhanced by APOE4","volume":"189","author":"Bilousova","year":"2019","journal-title":"Am. J. Pathol."},{"key":"10.1016\/j.neuron.2026.04.024_bib71","doi-asserted-by":"crossref","first-page":"1239","DOI":"10.1016\/j.neurobiolaging.2014.12.008","article-title":"APOE \u03b54 moderates amyloid-related memory decline in preclinical Alzheimer\u2019s disease","volume":"36","author":"Lim","year":"2015","journal-title":"Neurobiol. Aging"},{"key":"10.1016\/j.neuron.2026.04.024_bib72","doi-asserted-by":"crossref","first-page":"6820","DOI":"10.1073\/pnas.0900345106","article-title":"Fibrillar amyloid-\u03b2 burden in cognitively normal people at 3 levels of genetic risk for Alzheimer\u2019s disease","volume":"106","author":"Reiman","year":"2009","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"10.1016\/j.neuron.2026.04.024_bib73","doi-asserted-by":"crossref","first-page":"122","DOI":"10.1002\/ana.21843","article-title":"APOE predicts A\u03b2 but not tau Alzheimer\u2019s pathology in cognitively normal aging","volume":"67","author":"Morris","year":"2010","journal-title":"Ann. Neurol."},{"key":"10.1016\/j.neuron.2026.04.024_bib74","doi-asserted-by":"crossref","first-page":"1417","DOI":"10.1016\/j.jalz.2015.03.003","article-title":"APOE effect on Alzheimer\u2019s disease biomarkers in older adults with significant memory concern","volume":"11","author":"Risacher","year":"2015","journal-title":"Alzheimers. Dement."},{"key":"10.1016\/j.neuron.2026.04.024_bib75","doi-asserted-by":"crossref","first-page":"1997","DOI":"10.1017\/S0033291711000067","article-title":"Interaction effects of subjective memory impairment and ApoE4 genotype on episodic memory and hippocampal volume","volume":"41","author":"Striepens","year":"2011","journal-title":"Psychol. Med."},{"key":"10.1016\/j.neuron.2026.04.024_bib76","doi-asserted-by":"crossref","DOI":"10.3389\/fncom.2012.00052","article-title":"Progressive effect of beta amyloid peptides accumulation on CA1 pyramidal neurons: a model study suggesting possible treatments","volume":"6","author":"Culmone","year":"2012","journal-title":"Front. Comput. Neurosci."},{"key":"10.1016\/j.neuron.2026.04.024_bib77","doi-asserted-by":"crossref","first-page":"5157","DOI":"10.1523\/JNEUROSCI.1820-20.2021","article-title":"Amyloid-beta mediates homeostatic synaptic plasticity","volume":"41","author":"Galanis","year":"2021","journal-title":"J. Neurosci."},{"key":"10.1016\/j.neuron.2026.04.024_bib78","doi-asserted-by":"crossref","first-page":"1673","DOI":"10.1016\/j.neurobiolaging.2005.09.038","article-title":"Amyloid \u03b2 peptide as a physiological modulator of neuronal \u2018A\u2019-type K+ current","volume":"27","author":"Plant","year":"2006","journal-title":"Neurobiol. Aging"},{"key":"10.1016\/j.neuron.2026.04.024_bib79","doi-asserted-by":"crossref","DOI":"10.1038\/s41467-025-60370-8","article-title":"Variable and interactive effects of sex, APOE \u03b54 and TREM2 on the deposition of tau in entorhinal and neocortical regions","volume":"16","author":"Giorgio","year":"2025","journal-title":"Nat. Commun."},{"key":"10.1016\/j.neuron.2026.04.024_bib80","doi-asserted-by":"crossref","first-page":"2245","DOI":"10.1007\/s00259-020-05099-w","article-title":"The impact of demographic, clinical, genetic, and imaging variables on tau PET status","volume":"48","author":"Ossenkoppele","year":"2021","journal-title":"Eur. J. Nucl. Med. Mol. Imaging"},{"key":"10.1016\/j.neuron.2026.04.024_bib81","doi-asserted-by":"crossref","DOI":"10.1186\/s13024-022-00590-4","article-title":"APOE effects on regional tau in preclinical Alzheimer\u2019s disease","volume":"18","author":"Young","year":"2023","journal-title":"Mol. Neurodegener."},{"key":"10.1016\/j.neuron.2026.04.024_bib82","doi-asserted-by":"crossref","first-page":"470","DOI":"10.1001\/jamaneurol.2019.4421","article-title":"Association of apolipoprotein E \u03b54 with medial temporal tau independent of amyloid-\u03b2","volume":"77","author":"Therriault","year":"2020","journal-title":"JAMA Neurol."},{"key":"10.1016\/j.neuron.2026.04.024_bib83","article-title":"Tau accumulation and its spatial progression across the Alzheimer\u2019s disease spectrum","volume":"6","author":"St-Onge","year":"2024","journal-title":"Brain Commun."},{"key":"10.1016\/j.neuron.2026.04.024_bib84","doi-asserted-by":"crossref","first-page":"270","DOI":"10.1016\/j.jalz.2011.03.008","article-title":"The diagnosis of mild cognitive impairment due to Alzheimer\u2019s disease: Recommendations from the National Institute on Aging-Alzheimer\u2019s Association workgroups on diagnostic guidelines for Alzheimer\u2019s disease","volume":"7","author":"Albert","year":"2011","journal-title":"Alzheimers. Dement."},{"key":"10.1016\/j.neuron.2026.04.024_bib85","doi-asserted-by":"crossref","first-page":"1131","DOI":"10.1002\/ajmg.b.32495","article-title":"Apolipoprotein E genotypes and plasma levels in mild cognitive impairment conversion to Alzheimer\u2019s disease: A follow-up study","volume":"171","author":"Scarabino","year":"2016","journal-title":"Am. J. Med. Genet. B Neuropsychiatr. Genet."},{"key":"10.1016\/j.neuron.2026.04.024_bib86","doi-asserted-by":"crossref","first-page":"86","DOI":"10.1037\/a0030855","article-title":"The apolipoprotein E genotype predicts longitudinal transitions to mild cognitive impairment but not to Alzheimer\u2019s dementia: Findings from a nationally representative study","volume":"27","author":"Brainerd","year":"2013","journal-title":"Neuropsychology"},{"key":"10.1016\/j.neuron.2026.04.024_bib87","doi-asserted-by":"crossref","DOI":"10.1212\/WNL.0000000000005677","article-title":"APOE \u03b52\u03b54 genotype, incident AD and MCI, cognitive decline, and AD pathology in older adults","volume":"90","author":"Oveisgharan","year":"2018","journal-title":"Neurology"},{"key":"10.1016\/j.neuron.2026.04.024_bib88","doi-asserted-by":"crossref","first-page":"464","DOI":"10.21037\/qims.2020.01.14","article-title":"The effect of ApoE \u03b54 on clinical and structural MRI markers in prodromal Alzheimer\u2019s disease","volume":"10","author":"Zhang","year":"2020","journal-title":"Quant. Imaging Med. Surg."},{"key":"10.1016\/j.neuron.2026.04.024_bib89","doi-asserted-by":"crossref","DOI":"10.3389\/fnagi.2013.00011","article-title":"The role of apolipoprotein E (APOE) genotype in early mild cognitive impairment (E-MCI)","volume":"5","author":"Risacher","year":"2013","journal-title":"Front. Aging Neurosci."},{"key":"10.1016\/j.neuron.2026.04.024_bib90","doi-asserted-by":"crossref","first-page":"458","DOI":"10.1159\/000216841","article-title":"Rapid progression from mild cognitive impairment to Alzheimer\u2019s disease in subjects with elevated levels of tau in cerebrospinal fluid and the APOE \u03b54\/\u03b54 genotype","volume":"27","author":"Blom","year":"2009","journal-title":"Dement. Geriatr. Cogn. Disord."},{"key":"10.1016\/j.neuron.2026.04.024_bib91","doi-asserted-by":"crossref","first-page":"6448","DOI":"10.1073\/pnas.95.11.6448","article-title":"Diffusible, nonfibrillar ligands derived from A\u03b21\u201342 are potent central nervous system neurotoxins","volume":"95","author":"Lambert","year":"1998","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"10.1016\/j.neuron.2026.04.024_bib92","article-title":"A\u03b2 oligomers peak in early stages of Alzheimer\u2019s disease preceding tau pathology","volume":"16","author":"Bl\u00f6meke","year":"2024","journal-title":"Alzheimers Dement. (Amst)"},{"key":"10.1016\/j.neuron.2026.04.024_bib93","doi-asserted-by":"crossref","first-page":"1139","DOI":"10.1016\/j.neurobiolaging.2006.05.024","article-title":"A\u03b242 neurotoxicity in primary co-cultures: Effect of apoE isoform and A\u03b2 conformation","volume":"28","author":"Manelli","year":"2007","journal-title":"Neurobiol. Aging"},{"key":"10.1016\/j.neuron.2026.04.024_bib94","doi-asserted-by":"crossref","DOI":"10.3389\/fnagi.2018.00289","article-title":"Apolipoprotein E \u03b54 specifically modulates the hippocampus functional connectivity network in patients with amnestic mild cognitive impairment","volume":"10","author":"Zhu","year":"2018","journal-title":"Front. Aging Neurosci."},{"key":"10.1016\/j.neuron.2026.04.024_bib95","doi-asserted-by":"crossref","first-page":"1409","DOI":"10.3233\/JAD-160353","article-title":"Differential effects of APOE genotypes on the anterior and posterior subnetworks of default mode network in amnestic mild cognitive impairment","volume":"54","author":"Yuan","year":"2016","journal-title":"J. Alzheimers Dis."},{"key":"10.1016\/j.neuron.2026.04.024_bib96","doi-asserted-by":"crossref","first-page":"2332","DOI":"10.1212\/01.WNL.0000147469.18313.3B","article-title":"MCI conversion to dementia and the APOE genotype: a prediction study with FDG-PET","volume":"63","author":"Mosconi","year":"2004","journal-title":"Neurology"},{"key":"10.1016\/j.neuron.2026.04.024_bib97","doi-asserted-by":"crossref","first-page":"260","DOI":"10.1002\/glia.10153","article-title":"Microglia and inflammatory mechanisms in the clearance of amyloid \u03b2 peptide","volume":"40","author":"Rogers","year":"2002","journal-title":"Glia"},{"key":"10.1016\/j.neuron.2026.04.024_bib98","doi-asserted-by":"crossref","first-page":"1252","DOI":"10.1093\/brain\/aww017","article-title":"Early and protective microglial activation in Alzheimer\u2019s disease: a prospective study using 18 F-DPA-714 PET imaging","volume":"139","author":"Hamelin","year":"2016","journal-title":"Brain"},{"key":"10.1016\/j.neuron.2026.04.024_bib99","first-page":"792","article-title":"An early and late peak in microglial activation in Alzheimer\u2019s disease trajectory","volume":"140","author":"Fan","year":"2017","journal-title":"Brain"},{"key":"10.1016\/j.neuron.2026.04.024_bib100","doi-asserted-by":"crossref","DOI":"10.1126\/sciadv.ade1474","article-title":"APOE\u03b54 associates with microglial activation independently of A\u03b2 plaques and tau tangles","volume":"9","author":"Ferrari-Souza","year":"2023","journal-title":"Sci. Adv."},{"key":"10.1016\/j.neuron.2026.04.024_bib101","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\u2019s disease microglia","volume":"628","author":"Haney","year":"2024","journal-title":"Nature"},{"key":"10.1016\/j.neuron.2026.04.024_bib102","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\u2019s disease","volume":"169","author":"Keren-Shaul","year":"2017","journal-title":"Cell"},{"key":"10.1016\/j.neuron.2026.04.024_bib103","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":"Nat. Aging"},{"key":"10.1016\/j.neuron.2026.04.024_bib104","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"},{"key":"10.1016\/j.neuron.2026.04.024_bib105","doi-asserted-by":"crossref","first-page":"211","DOI":"10.1148\/radiol.13131041","article-title":"Mapping the effect of the apolipoprotein E genotype on 4-year atrophy rates in an Alzheimer disease\u2013related brain network","volume":"271","author":"Hostage","year":"2014","journal-title":"Radiology"},{"key":"10.1016\/j.neuron.2026.04.024_bib106","doi-asserted-by":"crossref","first-page":"229","DOI":"10.1212\/01.wnl.0000224748.48011.84","article-title":"Conversion to dementia from mild cognitive disorder: the Cache County Study","volume":"67","author":"Tschanz","year":"2006","journal-title":"Neurology"},{"key":"10.1016\/j.neuron.2026.04.024_bib107","doi-asserted-by":"crossref","first-page":"119","DOI":"10.3233\/JAD-2003-5206","article-title":"Apolipoprotein E \u03b54 in an autopsy series of various dementing disorders","volume":"5","author":"Nielsen","year":"2003","journal-title":"J. Alzheimers Dis."},{"key":"10.1016\/j.neuron.2026.04.024_bib108","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1007\/s00401-011-0910-3","article-title":"National Institute on Aging\u2013Alzheimer\u2019s Association guidelines for the neuropathologic assessment of Alzheimer\u2019s disease: a practical approach","volume":"123","author":"Montine","year":"2012","journal-title":"Acta Neuropathol."},{"key":"10.1016\/j.neuron.2026.04.024_bib109","doi-asserted-by":"crossref","DOI":"10.1101\/cshperspect.a006189","article-title":"Neuropathological Alterations in Alzheimer Disease","volume":"1","author":"Serrano-Pozo","year":"2011","journal-title":"Cold Spring Harb. Perspect. Med."},{"key":"10.1016\/j.neuron.2026.04.024_bib110","doi-asserted-by":"crossref","first-page":"300","DOI":"10.1136\/jnnp-2013-306485","article-title":"APOE associations with severe CAA-associated vasculopathic changes: collaborative meta-analysis","volume":"85","author":"Rannikm\u00e4e","year":"2014","journal-title":"J. Neurol. Neurosurg. Psychiatry"},{"key":"10.1016\/j.neuron.2026.04.024_bib111","doi-asserted-by":"crossref","first-page":"708","DOI":"10.1097\/NEN.0b013e31829a25b9","article-title":"APOE-\u03b52 and APOE-\u03b54 correlate with increased amyloid accumulation in cerebral vasculature","volume":"72","author":"Nelson","year":"2013","journal-title":"J. Neuropathol. Exp. Neurol."},{"key":"10.1016\/j.neuron.2026.04.024_bib112","doi-asserted-by":"crossref","first-page":"225","DOI":"10.1007\/s00401-016-1580-y","article-title":"Impact of sex and APOE4 on cerebral amyloid angiopathy in Alzheimer\u2019s disease","volume":"132","author":"Shinohara","year":"2016","journal-title":"Acta Neuropathol."},{"key":"10.1016\/j.neuron.2026.04.024_bib113","doi-asserted-by":"crossref","first-page":"109","DOI":"10.1038\/nrn3887","article-title":"Spreading of pathology in neurodegenerative diseases: a focus on human studies","volume":"16","author":"Brettschneider","year":"2015","journal-title":"Nat. Rev. Neurosci."},{"key":"10.1016\/j.neuron.2026.04.024_bib114","doi-asserted-by":"crossref","first-page":"1592","DOI":"10.1038\/s41591-021-01456-w","article-title":"Microglial activation and tau propagate jointly across Braak stages","volume":"27","author":"Pascoal","year":"2021","journal-title":"Nat. Med."},{"key":"10.1016\/j.neuron.2026.04.024_bib115","doi-asserted-by":"crossref","first-page":"2590","DOI":"10.1038\/s41591-025-03835-z","article-title":"APOE \u03b54 carriers share immune-related proteomic changes across neurodegenerative diseases","volume":"31","author":"Shvetcov","year":"2025","journal-title":"Nat. Med."},{"key":"10.1016\/j.neuron.2026.04.024_bib116","doi-asserted-by":"crossref","first-page":"439","DOI":"10.1111\/j.1750-3639.1998.tb00166.x","article-title":"Microglial activation in Alzheimer disease: association with APOE genotype","volume":"8","author":"Egensperger","year":"1998","journal-title":"Brain Pathol."},{"key":"10.1016\/j.neuron.2026.04.024_bib117","doi-asserted-by":"crossref","first-page":"383","DOI":"10.1007\/s004010051002","article-title":"Reactive microglia in aging and dementia: an immunohistochemical study of postmortem human brain tissue","volume":"97","author":"Overmyer","year":"1999","journal-title":"Acta Neuropathol."},{"key":"10.1016\/j.neuron.2026.04.024_bib118","doi-asserted-by":"crossref","DOI":"10.1186\/s12974-016-0601-z","article-title":"Microglial immunophenotype in dementia with Alzheimer\u2019s pathology","volume":"13","author":"Minett","year":"2016","journal-title":"J. Neuroinflamm."},{"key":"10.1016\/j.neuron.2026.04.024_bib119","doi-asserted-by":"crossref","DOI":"10.1186\/s13024-020-00376-6","article-title":"Mitochondria dysfunction in the pathogenesis of Alzheimer\u2019s disease: recent advances","volume":"15","author":"Wang","year":"2020","journal-title":"Mol. Neurodegener."},{"key":"10.1016\/j.neuron.2026.04.024_bib120","doi-asserted-by":"crossref","first-page":"157","DOI":"10.1038\/s41582-020-00435-y","article-title":"Neuroinflammation and microglial activation in Alzheimer disease: where do we go from here?","volume":"17","author":"Leng","year":"2021","journal-title":"Nat. Rev. Neurol."},{"key":"10.1016\/j.neuron.2026.04.024_bib121","doi-asserted-by":"crossref","first-page":"332","DOI":"10.1038\/s41586-019-1195-2","article-title":"Single-cell transcriptomic analysis of Alzheimer\u2019s disease","volume":"570","author":"Mathys","year":"2019","journal-title":"Nature"},{"key":"10.1016\/j.neuron.2026.04.024_bib122","doi-asserted-by":"crossref","DOI":"10.1016\/j.celrep.2023.112196","article-title":"APOE modulates microglial immunometabolism in response to age, amyloid pathology, and inflammatory challenge","volume":"42","author":"Lee","year":"2023","journal-title":"Cell Rep."},{"key":"10.1016\/j.neuron.2026.04.024_bib123","doi-asserted-by":"crossref","first-page":"209","DOI":"10.1002\/ana.10093","article-title":"Accelerated hippocampal atrophy in Alzheimer\u2019s disease with apolipoprotein E \u03b54 allele","volume":"51","author":"Mori","year":"2002","journal-title":"Ann. Neurol."},{"key":"10.1016\/j.neuron.2026.04.024_bib124","doi-asserted-by":"crossref","first-page":"65","DOI":"10.1016\/0306-4522(95)00014-A","article-title":"Volumes of hippocampus, amygdala and frontal lobe in Alzheimer patients with different apolipoprotein E genotypes","volume":"67","author":"Lehtovirta","year":"1995","journal-title":"Neuroscience"},{"key":"10.1016\/j.neuron.2026.04.024_bib125","doi-asserted-by":"crossref","first-page":"1825","DOI":"10.1212\/WNL.53.8.1825","article-title":"APOE-\u03b54 is associated with less frontal and more medial temporal lobe atrophy in AD","volume":"53","author":"Geroldi","year":"1999","journal-title":"Neurology"},{"key":"10.1016\/j.neuron.2026.04.024_bib126","doi-asserted-by":"crossref","first-page":"2527","DOI":"10.1523\/JNEUROSCI.4315-03.2004","article-title":"Neuron-specific apolipoprotein E4 proteolysis is associated with increased tau phosphorylation in brains of transgenic mice","volume":"24","author":"Brecht","year":"2004","journal-title":"J. Neurosci."},{"key":"10.1016\/j.neuron.2026.04.024_bib127","doi-asserted-by":"crossref","first-page":"10966","DOI":"10.1073\/pnas.1434398100","article-title":"Carboxyl-terminal-truncated apolipoprotein E4 causes Alzheimer\u2019s disease-like neurodegeneration and behavioral deficits in transgenic mice","volume":"100","author":"Harris","year":"2003","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"10.1016\/j.neuron.2026.04.024_bib128","doi-asserted-by":"crossref","first-page":"8838","DOI":"10.1073\/pnas.151254698","article-title":"Apolipoprotein E fragments present in Alzheimer\u2019s disease brains induce neurofibrillary tangle-like intracellular inclusions in neurons","volume":"98","author":"Huang","year":"2001","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"10.1016\/j.neuron.2026.04.024_bib129","doi-asserted-by":"crossref","first-page":"267","DOI":"10.14336\/AD.2015.1020","article-title":"Proteolytic cleavage of apolipoprotein E in the Down syndrome brain","volume":"7","author":"Day","year":"2016","journal-title":"Aging Dis."},{"key":"10.1016\/j.neuron.2026.04.024_bib130","doi-asserted-by":"crossref","DOI":"10.1016\/j.celrep.2023.113252","article-title":"APOE4-promoted gliosis and degeneration in tauopathy are ameliorated by pharmacological inhibition of HMGB1 release","volume":"42","author":"Koutsodendris","year":"2023","journal-title":"Cell Rep."},{"key":"10.1016\/j.neuron.2026.04.024_bib131","doi-asserted-by":"crossref","first-page":"701","DOI":"10.1038\/s41593-020-0624-8","article-title":"Disease-associated astrocytes in Alzheimer\u2019s disease and aging","volume":"23","author":"Habib","year":"2020","journal-title":"Nat. Neurosci."},{"key":"10.1016\/j.neuron.2026.04.024_bib132","doi-asserted-by":"crossref","first-page":"1608","DOI":"10.1523\/JNEUROSCI.2594-19.2020","article-title":"The dual role of microglia in the progression of Alzheimer\u2019s disease","volume":"40","author":"Onuska","year":"2020","journal-title":"J. Neurosci."},{"key":"10.1016\/j.neuron.2026.04.024_bib133","doi-asserted-by":"crossref","first-page":"7218","DOI":"10.1523\/JNEUROSCI.2574-18.2019","article-title":"Neuroinflammation and functional connectivity in Alzheimer\u2019s disease: interactive influences on cognitive performance","volume":"39","author":"Passamonti","year":"2019","journal-title":"J. Neurosci."},{"key":"10.1016\/j.neuron.2026.04.024_bib134","doi-asserted-by":"crossref","first-page":"425","DOI":"10.1038\/s41586-020-2453-z","article-title":"Physiological blood\u2013brain transport is impaired with age by a shift in transcytosis","volume":"583","author":"Yang","year":"2020","journal-title":"Nature"},{"key":"10.1016\/j.neuron.2026.04.024_bib135","doi-asserted-by":"crossref","first-page":"153","DOI":"10.1016\/j.immuni.2023.12.001","article-title":"An exhausted-like microglial population accumulates in aged and APOE4 genotype Alzheimer\u2019s brains","volume":"57","author":"Millet","year":"2024","journal-title":"Immunity"},{"key":"10.1016\/j.neuron.2026.04.024_bib136","doi-asserted-by":"crossref","DOI":"10.1016\/j.celrep.2022.111200","article-title":"APOE4 drives inflammation in human astrocytes via TAGLN3 repression and NF-\u03baB activation","volume":"40","author":"Arnaud","year":"2022","journal-title":"Cell Rep."},{"key":"10.1016\/j.neuron.2026.04.024_bib137","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"},{"key":"10.1016\/j.neuron.2026.04.024_bib138","doi-asserted-by":"crossref","DOI":"10.1016\/j.nbd.2022.105615","article-title":"APOE4 confers transcriptomic and functional alterations to primary mouse microglia","volume":"164","author":"Machlovi","year":"2022","journal-title":"Neurobiol. Dis."},{"key":"10.1016\/j.neuron.2026.04.024_bib139","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","year":"2012","journal-title":"Nature"},{"key":"10.1016\/j.neuron.2026.04.024_bib140","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\u2019s disease phenotypes in human iPSC-derived brain cell types","volume":"98","author":"Lin","year":"2018","journal-title":"Neuron"},{"key":"10.1016\/j.neuron.2026.04.024_bib141","doi-asserted-by":"crossref","first-page":"66","DOI":"10.1016\/j.nbd.2004.11.005","article-title":"Production and characterization of astrocyte-derived human apolipoprotein E isoforms from immortalized astrocytes and their interactions with amyloid-\u03b2","volume":"19","author":"Morikawa","year":"2005","journal-title":"Neurobiol. Dis."},{"key":"10.1016\/j.neuron.2026.04.024_bib142","article-title":"Human-lineage-specific genomic elements are associated with neurodegenerative disease and APOE transcript usage","volume":"12","author":"Chen","year":"2021","journal-title":"Nat. Commun."},{"key":"10.1016\/j.neuron.2026.04.024_bib143","doi-asserted-by":"crossref","first-page":"6002","DOI":"10.1038\/s41380-020-00956-4","article-title":"C\/EBP\u03b2 is a key transcription factor for APOE and preferentially mediates ApoE4 expression in Alzheimer\u2019s disease","volume":"26","author":"Xia","year":"2021","journal-title":"Mol. Psychiatry"},{"key":"10.1016\/j.neuron.2026.04.024_bib144","doi-asserted-by":"crossref","first-page":"12497","DOI":"10.1093\/nar\/gkac1107","article-title":"A common transcriptional mechanism involving R-loop and RNA abasic site regulates an enhancer RNA of APOE","volume":"50","author":"Watts","year":"2022","journal-title":"Nucleic Acids Res."},{"key":"10.1016\/j.neuron.2026.04.024_bib145","article-title":"Dent","volume":"37","author":"Aery Jones","year":"2021","journal-title":"Cell Rep."},{"key":"10.1016\/j.neuron.2026.04.024_bib146","article-title":"Apolipoprotein E: isoform specific differences in tertiary structure and interaction with amyloid-\u03b2 in human Alzheimer brain","volume":"6","author":"Jones","year":"2011","journal-title":"PLoS One"},{"key":"10.1016\/j.neuron.2026.04.024_bib147","doi-asserted-by":"crossref","DOI":"10.1038\/s41598-019-40438-4","article-title":"ApoE-fragment\/A\u03b2 heteromers in the brain of patients with Alzheimer\u2019s disease","volume":"9","author":"Mouchard","year":"2019","journal-title":"Sci. Rep."},{"key":"10.1016\/j.neuron.2026.04.024_bib148","doi-asserted-by":"crossref","first-page":"257","DOI":"10.1016\/j.neurobiolaging.2009.02.006","article-title":"Isoform-specific proteolysis of apolipoprotein-E in the brain","volume":"32","author":"Elliott","year":"2011","journal-title":"Neurobiol. Aging"},{"key":"10.1016\/j.neuron.2026.04.024_bib149","doi-asserted-by":"crossref","first-page":"951","DOI":"10.1016\/S0002-9440(10)64963-2","article-title":"Expression of human apolipoprotein E4 in neurons causes hyperphosphorylation of protein tau in the brains of transgenic mice","volume":"156","author":"Tesseur","year":"2000","journal-title":"Am. J. Pathol."},{"key":"10.1016\/j.neuron.2026.04.024_bib150","doi-asserted-by":"crossref","first-page":"326","DOI":"10.1006\/exnr.2001.7715","article-title":"Behavioral phenotyping of GFAP-ApoE3 and -ApoE4 transgenic mice: ApoE4 mice show profound working memory impairments in the absence of Alzheimer\u2019s-like neuropathology","volume":"170","author":"Hartman","year":"2001","journal-title":"Exp. Neurol."},{"key":"10.1016\/j.neuron.2026.04.024_bib151","doi-asserted-by":"crossref","first-page":"4236","DOI":"10.1073\/pnas.1018381108","article-title":"C-terminal-truncated apolipoprotein (apo) E4 inefficiently clears amyloid-\u03b2 (A\u03b2) and acts in concert with A\u03b2 to elicit neuronal and behavioral deficits in mice","volume":"108","author":"Bien-Ly","year":"2011","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"10.1016\/j.neuron.2026.04.024_bib152","doi-asserted-by":"crossref","first-page":"370","DOI":"10.1016\/j.bbadis.2011.11.005","article-title":"PET amyloid-beta imaging in preclinical Alzheimer\u2019s disease","volume":"1822","author":"Vlassenko","year":"2012","journal-title":"Biochim. Biophys. Acta"},{"key":"10.1016\/j.neuron.2026.04.024_bib153","doi-asserted-by":"crossref","first-page":"608","DOI":"10.1016\/j.neuron.2014.10.038","article-title":"The evolution of preclinical Alzheimer\u2019s disease: implications for prevention trials","volume":"84","author":"Sperling","year":"2014","journal-title":"Neuron"},{"key":"10.1016\/j.neuron.2026.04.024_bib154","doi-asserted-by":"crossref","first-page":"631","DOI":"10.1212\/WNL.42.3.631","article-title":"Neurofibrillary tangles but not senile plaques parallel duration and severity of Alzheimer\u2019s disease","volume":"42","author":"Arriagada","year":"1992","journal-title":"Neurology"},{"key":"10.1016\/j.neuron.2026.04.024_bib155","doi-asserted-by":"crossref","first-page":"1551","DOI":"10.1093\/brain\/aww027","article-title":"Tau PET patterns mirror clinical and neuroanatomical variability in Alzheimer\u2019s disease","volume":"139","author":"Ossenkoppele","year":"2016","journal-title":"Brain"},{"key":"10.1016\/j.neuron.2026.04.024_bib156","doi-asserted-by":"crossref","DOI":"10.1126\/scitranslmed.aaf2362","article-title":"Tau and A\u03b2 imaging, CSF measures, and cognition in Alzheimer\u2019s disease","volume":"8","author":"Brier","year":"2016","journal-title":"Sci. Transl. Med."},{"key":"10.1016\/j.neuron.2026.04.024_bib157","doi-asserted-by":"crossref","first-page":"476","DOI":"10.1038\/s41583-022-00599-0","article-title":"The role of inhibitory circuits in hippocampal memory processing","volume":"23","author":"Topolnik","year":"2022","journal-title":"Nat. Rev. Neurosci."},{"key":"10.1016\/j.neuron.2026.04.024_bib158","doi-asserted-by":"crossref","DOI":"10.7554\/eLife.36011","article-title":"Oscillatory hyperactivity and hyperconnectivity in young APOE-\u03f54 carriers and hypoconnectivity in Alzheimer\u2019s disease","volume":"8","author":"Koelewijn","year":"2019","journal-title":"eLife"},{"key":"10.1016\/j.neuron.2026.04.024_bib159","doi-asserted-by":"crossref","first-page":"167","DOI":"10.1016\/j.cortex.2014.04.006","article-title":"Aberrant functional connectivity in Papez circuit correlates with memory performance in cognitively intact middle-aged APOE4 carriers","volume":"57","author":"Li","year":"2014","journal-title":"Cortex"},{"key":"10.1016\/j.neuron.2026.04.024_bib160","doi-asserted-by":"crossref","first-page":"17680","DOI":"10.1523\/JNEUROSCI.4740-11.2011","article-title":"Hippocampal hyperactivation associated with cortical thinning in Alzheimer\u2019s disease signature regions in non-demented elderly adults","volume":"31","author":"Putcha","year":"2011","journal-title":"J. Neurosci."},{"key":"10.1016\/j.neuron.2026.04.024_bib161","doi-asserted-by":"crossref","first-page":"630","DOI":"10.1136\/jnnp.2007.124149","article-title":"Hippocampal activation in adults with mild cognitive impairment predicts subsequent cognitive decline","volume":"79","author":"Miller","year":"2008","journal-title":"J. Neurol. Neurosurg. Psychiatry"},{"key":"10.1016\/j.neuron.2026.04.024_bib162","doi-asserted-by":"crossref","first-page":"1603","DOI":"10.1176\/ajp.2006.163.9.1603","article-title":"Increased brain activation during working memory in cognitively intact adults with the APOE \u03b54 allele","volume":"163","author":"Wishart","year":"2006","journal-title":"Am. J. Psychiatry"},{"key":"10.1016\/j.neuron.2026.04.024_bib163","doi-asserted-by":"crossref","first-page":"1881","DOI":"10.1001\/archneur.62.12.1881","article-title":"Identification of Alzheimer disease risk by functional magnetic resonance imaging","volume":"62","author":"Fleisher","year":"2005","journal-title":"Arch. Neurol."},{"key":"10.1016\/j.neuron.2026.04.024_bib164","doi-asserted-by":"crossref","first-page":"1158","DOI":"10.1001\/jamaneurol.2013.136","article-title":"Seizures and epileptiform activity in the early stages of Alzheimer disease","volume":"70","author":"Vossel","year":"2013","journal-title":"JAMA Neurol."},{"key":"10.1016\/j.neuron.2026.04.024_bib165","doi-asserted-by":"crossref","first-page":"120","DOI":"10.1016\/j.brainres.2012.05.048","article-title":"Emergence of a seizure phenotype in aged apolipoprotein epsilon 4 targeted replacement mice","volume":"1467","author":"Hunter","year":"2012","journal-title":"Brain Res."},{"key":"10.1016\/j.neuron.2026.04.024_bib166","doi-asserted-by":"crossref","first-page":"1025","DOI":"10.1126\/science.1589772","article-title":"High-frequency network oscillation in the hippocampus","volume":"256","author":"Buzs\u00e1ki","year":"1992","journal-title":"Science"},{"key":"10.1016\/j.neuron.2026.04.024_bib167","doi-asserted-by":"crossref","first-page":"700","DOI":"10.1016\/j.neuron.2012.06.014","article-title":"Transient slow gamma synchrony underlies hippocampal memory replay","volume":"75","author":"Carr","year":"2012","journal-title":"Neuron"},{"key":"10.1016\/j.neuron.2026.04.024_bib168","doi-asserted-by":"crossref","first-page":"932","DOI":"10.1038\/s43587-021-00122-7","article-title":"Experimental and real-world evidence supporting the computational repurposing of bumetanide for APOE4-related Alzheimer\u2019s disease","volume":"1","author":"Taubes","year":"2021","journal-title":"Nat. Aging"},{"key":"10.1016\/j.neuron.2026.04.024_bib169","doi-asserted-by":"crossref","first-page":"748","DOI":"10.1111\/cns.12720","article-title":"Hippocampal synaptic and neural network deficits in young mice carrying the human APOE4 gene","volume":"23","author":"Sun","year":"2017","journal-title":"CNS Neurosci. Ther."},{"key":"10.1016\/j.neuron.2026.04.024_bib170","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"},{"key":"10.1016\/j.neuron.2026.04.024_bib171","doi-asserted-by":"crossref","DOI":"10.1126\/scitranslmed.abb1717","article-title":"Endosomal recycling reconciles the Alzheimer\u2019s disease paradox","volume":"12","author":"Small","year":"2020","journal-title":"Sci. Transl. Med."},{"key":"10.1016\/j.neuron.2026.04.024_bib172","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","year":"2010","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"10.1016\/j.neuron.2026.04.024_bib173","doi-asserted-by":"crossref","first-page":"3240","DOI":"10.1080\/15548627.2025.2576613","article-title":"Lysosomal proteomics reveals mechanisms of neuronal apoE4-associated lysosomal dysfunction","volume":"21","author":"Krogsaeter","year":"2025","journal-title":"Autophagy"},{"key":"10.1016\/j.neuron.2026.04.024_bib174","doi-asserted-by":"crossref","DOI":"10.3389\/fnins.2017.00702","article-title":"The endosomal\u2013lysosomal pathway is dysregulated by APOE4 expression in vivo","volume":"11","author":"Nuriel","year":"2017","journal-title":"Front. Neurosci."},{"key":"10.1016\/j.neuron.2026.04.024_bib175","doi-asserted-by":"crossref","first-page":"688","DOI":"10.1038\/s41593-022-01084-8","article-title":"Faulty autolysosome acidification in Alzheimer\u2019s disease mouse models induces autophagic build-up of A\u03b2 in neurons, yielding senile plaques","volume":"25","author":"Lee","year":"2022","journal-title":"Nat. Neurosci."},{"key":"10.1016\/j.neuron.2026.04.024_bib176","article-title":"APOE4\u2013A\u03b2 synergy drives brain network dysfunction and neuronal lysosomal-ER proteostasis dysregulation a preclinical Alzheimer\u2019s disease model","author":"Shin","year":"2025","journal-title":"bioRxiv"},{"key":"10.1016\/j.neuron.2026.04.024_bib177","doi-asserted-by":"crossref","DOI":"10.7554\/eLife.72034","article-title":"NHE6 depletion corrects ApoE4-mediated synaptic impairments and reduces amyloid plaque load","volume":"10","author":"Pohlkamp","year":"2021","journal-title":"eLife"},{"key":"10.1016\/j.neuron.2026.04.024_bib178","doi-asserted-by":"crossref","DOI":"10.7554\/eLife.40048","article-title":"Reversal of ApoE4-induced recycling block as a novel prevention approach for Alzheimer\u2019s disease","volume":"7","author":"Xian","year":"2018","journal-title":"eLife"},{"key":"10.1016\/j.neuron.2026.04.024_bib179","doi-asserted-by":"crossref","first-page":"1351","DOI":"10.1016\/j.cmet.2024.03.014","article-title":"Microglial lipid droplet accumulation in tauopathy brain is regulated by neuronal AMPK","volume":"36","author":"Li","year":"2024","journal-title":"Cell Metab."},{"key":"10.1016\/j.neuron.2026.04.024_bib180","doi-asserted-by":"crossref","DOI":"10.1038\/s41467-025-60402-3","article-title":"Endolysosomal processing of neuron-derived signaling lipids regulates autophagy and lipid droplet degradation in astrocytes","volume":"16","author":"Bhupana","year":"2025","journal-title":"Nat. Commun."},{"key":"10.1016\/j.neuron.2026.04.024_bib181","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.neuron.2026.04.024_bib182","article-title":"Neuronal APOE4 drives damaging lipid accumulation via contact-dependent neuron-oligodendrocyte-microglia interaction in Alzheimer\u2019s disease","author":"Kim","year":"2025","journal-title":"bioRxiv"},{"key":"10.1016\/j.neuron.2026.04.024_bib183","doi-asserted-by":"crossref","first-page":"e2404","DOI":"10.1212\/WNL.0000000000009582","article-title":"Effect of ApoE isoforms on mitochondria in Alzheimer disease","volume":"94","author":"Yin","year":"2020","journal-title":"Neurology"},{"key":"10.1016\/j.neuron.2026.04.024_bib184","doi-asserted-by":"crossref","first-page":"752","DOI":"10.1056\/NEJM199603213341202","article-title":"Preclinical evidence of Alzheimer\u2019s disease in persons homozygous for the \u03b54 allele for apolipoprotein E","volume":"334","author":"Reiman","year":"1996","journal-title":"N. Engl. J. Med."},{"key":"10.1016\/j.neuron.2026.04.024_bib185","doi-asserted-by":"crossref","first-page":"6037","DOI":"10.1073\/pnas.090106797","article-title":"Cerebral metabolic and cognitive decline in persons at genetic risk for Alzheimer\u2019s disease","volume":"97","author":"Small","year":"2000","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"10.1016\/j.neuron.2026.04.024_bib186","first-page":"397","article-title":"Human gray and white matter metabolomics to differentiate APOE and stage dependent changes in Alzheimer\u2019s disease","volume":"3","author":"Hammond","year":"2021","journal-title":"J. Cell Immunol."},{"key":"10.1016\/j.neuron.2026.04.024_bib187","doi-asserted-by":"crossref","DOI":"10.1016\/j.nbd.2022.105781","article-title":"Mitochondrial function and A\u03b2 in Alzheimer\u2019s disease postmortem brain","volume":"171","author":"Troutwine","year":"2022","journal-title":"Neurobiol. Dis."},{"key":"10.1016\/j.neuron.2026.04.024_bib188","doi-asserted-by":"crossref","first-page":"307","DOI":"10.3233\/JAD-2010-100129","article-title":"Reduced posterior cingulate mitochondrial activity in expired young adult carriers of the APOE \u03b54 allele, the major late-onset Alzheimer\u2019s susceptibility gene","volume":"22","author":"Valla","year":"2010","journal-title":"J. Alzheimers Dis."},{"key":"10.1016\/j.neuron.2026.04.024_bib189","doi-asserted-by":"crossref","first-page":"266","DOI":"10.1136\/jnnp-2013-305858","article-title":"Greater medial temporal hypometabolism and lower cortical amyloid burden in ApoE4-positive AD patients","volume":"85","author":"Lehmann","year":"2014","journal-title":"J. Neurol. Neurosurg. Psychiatry"},{"key":"10.1016\/j.neuron.2026.04.024_bib190","doi-asserted-by":"crossref","first-page":"861","DOI":"10.3233\/JAD-190074","article-title":"The effects of APOE4 on mitochondrial dynamics and proteins in vivo","volume":"70","author":"Simonovitch","year":"2019","journal-title":"J. Alzheimers Dis."},{"key":"10.1016\/j.neuron.2026.04.024_bib191","doi-asserted-by":"crossref","first-page":"11148","DOI":"10.18632\/aging.102516","article-title":"Apolipoprotein E regulates mitochondrial function through the PGC-1\u03b1-sirtuin 3 pathway","volume":"11","author":"Yin","year":"2019","journal-title":"Aging"},{"key":"10.1016\/j.neuron.2026.04.024_bib192","doi-asserted-by":"crossref","first-page":"991","DOI":"10.3233\/JAD-181184","article-title":"Neuronal apolipoprotein E4 expression results in proteome-wide alterations and compromises bioenergetic capacity by disrupting mitochondrial function","volume":"68","author":"Orr","year":"2019","journal-title":"J. Alzheimers Dis."},{"key":"10.1016\/j.neuron.2026.04.024_bib193","doi-asserted-by":"crossref","first-page":"591","DOI":"10.3233\/JAD-221177","article-title":"Mitochondria profoundly influence apolipoprotein E biology","volume":"92","author":"Gabrielli","year":"2023","journal-title":"J. Alzheimers Dis."},{"key":"10.1016\/j.neuron.2026.04.024_bib194","doi-asserted-by":"crossref","first-page":"5215","DOI":"10.1074\/jbc.M110.151084","article-title":"Apolipoprotein E4 domain interaction mediates detrimental effects on mitochondria and is a potential therapeutic target for Alzheimer disease","volume":"286","author":"Chen","year":"2011","journal-title":"J. Biol. Chem."},{"key":"10.1016\/j.neuron.2026.04.024_bib195","doi-asserted-by":"crossref","first-page":"18694","DOI":"10.1073\/pnas.0508254102","article-title":"Lipid- and receptor-binding regions of apolipoprotein E4 fragments act in concert to cause mitochondrial dysfunction and neurotoxicity","volume":"102","author":"Chang","year":"2005","journal-title":"Proc. Natl. Acad. Sci. US."},{"key":"10.1016\/j.neuron.2026.04.024_bib196","doi-asserted-by":"crossref","first-page":"17217","DOI":"10.1074\/jbc.M110.217380","article-title":"Structure-dependent impairment of intracellular apolipoprotein E4 trafficking and its detrimental effects are rescued by small-molecule structure correctors","volume":"286","author":"Brodbeck","year":"2011","journal-title":"J. Biol. Chem."},{"key":"10.1016\/j.neuron.2026.04.024_bib197","doi-asserted-by":"crossref","first-page":"8997","DOI":"10.1021\/jm3008618","article-title":"Small-molecule structure correctors target abnormal protein structure and function: structure corrector rescue of apolipoprotein E4\u2013associated neuropathology","volume":"55","author":"Mahley","year":"2012","journal-title":"J. Med. Chem."},{"key":"10.1016\/j.neuron.2026.04.024_bib198","doi-asserted-by":"crossref","first-page":"885","DOI":"10.1016\/S0006-291X(84)80190-4","article-title":"Alzheimer\u2019s disease: Initial report of the purification and characterization of a novel cerebrovascular amyloid protein","volume":"120","author":"Glenner","year":"1984","journal-title":"Biochem. Biophys. Res. Commun."},{"key":"10.1016\/j.neuron.2026.04.024_bib199","doi-asserted-by":"crossref","first-page":"S183","DOI":"10.1194\/jlr.R800069-JLR200","article-title":"Apolipoprotein E: structure determines function, from atherosclerosis to Alzheimer\u2019s disease to AIDS","volume":"50","author":"Mahley","year":"2009","journal-title":"J. Lipid Res."},{"key":"10.1016\/j.neuron.2026.04.024_bib200","doi-asserted-by":"crossref","DOI":"10.1186\/s13024-022-00574-4","article-title":"ApoE in Alzheimer\u2019s disease: pathophysiology and therapeutic strategies","volume":"17","author":"Raulin","year":"2022","journal-title":"Mol. Neurodegener."},{"key":"10.1016\/j.neuron.2026.04.024_bib201","doi-asserted-by":"crossref","first-page":"1585","DOI":"10.1096\/fj.10-175976","article-title":"High ability of apolipoprotein E4 to stabilize amyloid-\u03b2 peptide oligomers, the pathological entities responsible for Alzheimer\u2019s disease","volume":"25","author":"Cerf","year":"2011","journal-title":"FASEB J."},{"key":"10.1016\/j.neuron.2026.04.024_bib202","doi-asserted-by":"crossref","first-page":"263","DOI":"10.1038\/ng1197-263","article-title":"Lack of apolipoprotein E dramatically reduces amyloid \u03b2-peptide deposition","volume":"17","author":"Bales","year":"1997","journal-title":"Nat. Genet."},{"key":"10.1016\/j.neuron.2026.04.024_bib203","doi-asserted-by":"crossref","first-page":"15233","DOI":"10.1073\/pnas.96.26.15233","article-title":"Apolipoprotein E is essential for amyloid deposition in the APPV717F transgenic mouse model of Alzheimer\u2019s disease","volume":"96","author":"Bales","year":"1999","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"10.1016\/j.neuron.2026.04.024_bib204","doi-asserted-by":"crossref","first-page":"4803","DOI":"10.1523\/JNEUROSCI.0033-12.2012","article-title":"Reducing human apolipoprotein E levels attenuates age-dependent A\u03b2 accumulation in mutant human amyloid precursor protein transgenic mice","volume":"32","author":"Bien-Ly","year":"2012","journal-title":"J. Neurosci."},{"key":"10.1016\/j.neuron.2026.04.024_bib205","doi-asserted-by":"crossref","first-page":"18007","DOI":"10.1523\/JNEUROSCI.3773-11.2011","article-title":"Haploinsufficiency of human APOE reduces amyloid deposition in a mouse model of amyloid-\u03b2 amyloidosis","volume":"31","author":"Kim","year":"2011","journal-title":"J. Neurosci."},{"key":"10.1016\/j.neuron.2026.04.024_bib206","doi-asserted-by":"crossref","first-page":"535","DOI":"10.1016\/j.jalz.2018.02.018","article-title":"NIA-AA research framework: toward a biological definition of Alzheimer\u2019s disease","volume":"14","author":"Jack","year":"2018","journal-title":"Alzheimers. Dement."},{"key":"10.1016\/j.neuron.2026.04.024_bib207","doi-asserted-by":"crossref","first-page":"650","DOI":"10.1002\/ana.21696","article-title":"Apolipoprotein E\u2013dependent accumulation of Alzheimer disease\u2013related lesions begins in middle age","volume":"65","author":"Kok","year":"2009","journal-title":"Ann. Neurol."},{"key":"10.1016\/j.neuron.2026.04.024_bib208","doi-asserted-by":"crossref","first-page":"14088","DOI":"10.1073\/pnas.96.24.14088","article-title":"Neuronal overexpression of mutant amyloid precursor protein results in prominent deposition of cerebrovascular amyloid","volume":"96","author":"Calhoun","year":"1999","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"10.1016\/j.neuron.2026.04.024_bib209","doi-asserted-by":"crossref","first-page":"31407","DOI":"10.1074\/jbc.271.49.31407","article-title":"\u03b2-Secretase processing of the \u03b2-amyloid precursor protein in transgenic mice is efficient in neurons but inefficient in astrocytes","volume":"271","author":"Zhao","year":"1996","journal-title":"J. Biol. Chem."},{"key":"10.1016\/j.neuron.2026.04.024_bib210","doi-asserted-by":"crossref","first-page":"523","DOI":"10.1007\/s00401-010-0679-9","article-title":"Intraneuronal \u03b2-amyloid accumulation and synapse pathology in Alzheimer\u2019s disease","volume":"119","author":"Gouras","year":"2010","journal-title":"Acta Neuropathol."},{"key":"10.1016\/j.neuron.2026.04.024_bib211","doi-asserted-by":"crossref","first-page":"499","DOI":"10.1038\/nrn2168","article-title":"Intracellular amyloid-\u03b2 in Alzheimer\u2019s disease","volume":"8","author":"LaFerla","year":"2007","journal-title":"Nat. Rev. Neurosci."},{"key":"10.1016\/j.neuron.2026.04.024_bib212","doi-asserted-by":"crossref","first-page":"120","DOI":"10.1046\/j.1365-2559.2001.01082.x","article-title":"Evidence that neurones accumulating amyloid can undergo lysis to form amyloid plaques in Alzheimer\u2019s disease","volume":"38","author":"D\u2019Andrea","year":"2001","journal-title":"Histopathology"},{"key":"10.1016\/j.neuron.2026.04.024_bib213","doi-asserted-by":"crossref","first-page":"15","DOI":"10.1016\/S0002-9440(10)64700-1","article-title":"Intraneuronal A\u03b242 accumulation in human brain","volume":"156","author":"Gouras","year":"2000","journal-title":"Am. J. Pathol."},{"key":"10.1016\/j.neuron.2026.04.024_bib214","doi-asserted-by":"crossref","first-page":"555","DOI":"10.1007\/s00401-010-0666-1","article-title":"Accumulation of intraneuronal A\u03b2 correlates with ApoE4 genotype","volume":"119","author":"Christensen","year":"2010","journal-title":"Acta Neuropathol."},{"key":"10.1016\/j.neuron.2026.04.024_bib215","doi-asserted-by":"crossref","first-page":"36180","DOI":"10.1074\/jbc.M604436200","article-title":"Apolipoprotein E and low density lipoprotein receptor-related protein facilitate intraneuronal A\u03b242 accumulation in amyloid model mice","volume":"281","author":"Zerbinatti","year":"2006","journal-title":"J. Biol. Chem."},{"key":"10.1016\/j.neuron.2026.04.024_bib216","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\u2019s disease model","volume":"32","author":"Rao","year":"2025","journal-title":"Cell Stem Cell"},{"key":"10.1016\/j.neuron.2026.04.024_bib217","doi-asserted-by":"crossref","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."},{"key":"10.1016\/j.neuron.2026.04.024_bib218","doi-asserted-by":"crossref","first-page":"845","DOI":"10.1038\/s41580-024-00753-9","article-title":"Cellular and pathological functions of tau","volume":"25","author":"Parra Bravo","year":"2024","journal-title":"Nat. Rev. Mol. Cell Biol."},{"key":"10.1016\/j.neuron.2026.04.024_bib219","doi-asserted-by":"crossref","first-page":"5","DOI":"10.1007\/s40259-023-00633-2","article-title":"Anti-amyloid monoclonal antibodies for the treatment of Alzheimer\u2019s disease","volume":"38","author":"Cummings","year":"2024","journal-title":"BioDrugs"},{"key":"10.1016\/j.neuron.2026.04.024_bib220","doi-asserted-by":"crossref","first-page":"1680","DOI":"10.1038\/s41591-019-0611-3","article-title":"Resistance to autosomal dominant Alzheimer\u2019s disease in an APOE3 Christchurch homozygote: a case report","volume":"25","author":"Arboleda-Velasquez","year":"2019","journal-title":"Nat. Med."},{"key":"10.1016\/j.neuron.2026.04.024_bib221","doi-asserted-by":"crossref","first-page":"523","DOI":"10.1038\/nature24016","article-title":"ApoE4 markedly exacerbates tau-mediated neurodegeneration in a mouse model of tauopathy","volume":"549","author":"Shi","year":"2017","journal-title":"Nature"},{"key":"10.1016\/j.neuron.2026.04.024_bib222","doi-asserted-by":"crossref","first-page":"106","DOI":"10.1016\/j.brainres.2012.08.003","article-title":"Identification of an amino-terminal fragment of apolipoprotein E4 that localizes to neurofibrillary tangles of the Alzheimer\u2019s disease brain","volume":"1475","author":"Rohn","year":"2012","journal-title":"Brain Res."},{"key":"10.1016\/j.neuron.2026.04.024_bib223","doi-asserted-by":"crossref","DOI":"10.1186\/s13195-024-01642-1","article-title":"Longitudinal trajectory of plasma p-tau217 in cognitively unimpaired subjects","volume":"16","author":"Mart\u00ednez-Dubarbie","year":"2024","journal-title":"Alzheimers Res. Ther."},{"key":"10.1016\/j.neuron.2026.04.024_bib224","doi-asserted-by":"crossref","first-page":"1309","DOI":"10.3233\/JAD-210673","article-title":"Association of APOE \u03f54 and plasma p-tau181 with preclinical Alzheimer\u2019s disease and longitudinal change in hippocampus function","volume":"85","author":"Salami","year":"2022","journal-title":"J. Alzheimers Dis."},{"key":"10.1016\/j.neuron.2026.04.024_bib225","doi-asserted-by":"crossref","first-page":"477","DOI":"10.1007\/s00702-022-02461-0","article-title":"Don\u2019t forget about tau: the effects of ApoE4 genotype on Alzheimer\u2019s disease cerebrospinal fluid biomarkers in subjects with mild cognitive impairment\u2014data from the Dementia Competence Network","volume":"129","author":"Benson","year":"2022","journal-title":"J. Neural Transm. (Vienna)"},{"key":"10.1016\/j.neuron.2026.04.024_bib226","doi-asserted-by":"crossref","DOI":"10.1126\/scitranslmed.abn7273","article-title":"Network Tau spreading is vulnerable to the expression gradients of APOE and glutamatergic-related genes","volume":"14","author":"Montal","year":"2022","journal-title":"Sci. Transl. Med."},{"key":"10.1016\/j.neuron.2026.04.024_bib227","doi-asserted-by":"crossref","first-page":"15181","DOI":"10.1523\/JNEUROSCI.1542-12.2012","article-title":"Apolipoprotein E, especially apolipoprotein E4, increases the oligomerization of amyloid \u03b2 peptide","volume":"32","author":"Hashimoto","year":"2012","journal-title":"J. Neurosci."},{"key":"10.1016\/j.neuron.2026.04.024_bib228","doi-asserted-by":"crossref","first-page":"2012","DOI":"10.2353\/ajpath.2007.070403","article-title":"Induction of tau pathology by intracerebral infusion of amyloid-\u03b2-containing brain extract and by amyloid-\u03b2 deposition in APP \u00d7 tau transgenic mice","volume":"171","author":"Bolmont","year":"2007","journal-title":"Am. J. Pathol."},{"key":"10.1016\/j.neuron.2026.04.024_bib229","doi-asserted-by":"crossref","DOI":"10.1126\/sciadv.aaz2387","article-title":"A\u03b2 deposition is associated with increases in soluble and phosphorylated tau that precede a positive Tau PET in Alzheimer\u2019s disease","volume":"6","author":"Mattsson-Carlgren","year":"2020","journal-title":"Sci. Adv."},{"key":"10.1016\/j.neuron.2026.04.024_bib230","doi-asserted-by":"crossref","first-page":"549","DOI":"10.1007\/s00401-015-1525-x","article-title":"Heterotypic seeding of Tau fibrillization by pre-aggregated Abeta provides potent seeds for prion-like seeding and propagation of Tau-pathology in vivo","volume":"131","author":"Vasconcelos","year":"2016","journal-title":"Acta Neuropathol."},{"key":"10.1016\/j.neuron.2026.04.024_bib231","doi-asserted-by":"crossref","DOI":"10.1002\/alz.046206","article-title":"ApoE4 associated with higher tau accumulation independent of amyloid burden","volume":"16","author":"Neitzel","year":"2020","journal-title":"Alzheimer Dement"},{"key":"10.1016\/j.neuron.2026.04.024_bib232","doi-asserted-by":"crossref","first-page":"18","DOI":"10.1002\/acn3.51695","article-title":"Plasma phosphorylated tau181 predicts cognitive and functional decline","volume":"10","author":"Tropea","year":"2023","journal-title":"Ann. Clin. Transl. Neurol."},{"key":"10.1016\/j.neuron.2026.04.024_bib233","doi-asserted-by":"crossref","first-page":"272","DOI":"10.1007\/BF02829548","article-title":"Effect of truncated-ApoE4 overexpression on tau phosphorylation in cultured N2a cells","volume":"26","author":"Zhou","year":"2006","journal-title":"J. Huazhong Univ. Sci. Technolog. Med. Sci."},{"key":"10.1016\/j.neuron.2026.04.024_bib234","doi-asserted-by":"crossref","DOI":"10.1371\/journal.pone.0021050","article-title":"P301S mutant human tau transgenic mice manifest early symptoms of human tauopathies with dementia and altered sensorimotor gating","volume":"6","author":"Takeuchi","year":"2011","journal-title":"PLOS One"},{"key":"10.1016\/j.neuron.2026.04.024_bib235","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","year":"2021","journal-title":"Ann. Neurol."},{"key":"10.1016\/j.neuron.2026.04.024_bib236","doi-asserted-by":"crossref","DOI":"10.1002\/alz.088537","article-title":"ApoE4 antibody ameliorates cognitive impairments and synapse loss in ApoE4\/Tau-P301S mice","volume":"20","author":"Song","year":"2024","journal-title":"Alzheimer Dement."},{"key":"10.1016\/j.neuron.2026.04.024_bib237","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. USA"},{"key":"10.1016\/j.neuron.2026.04.024_bib238","doi-asserted-by":"crossref","DOI":"10.1038\/s41598-021-82901-1","article-title":"Astrocytic expression of the Alzheimer\u2019s disease risk allele, ApoE\u03b54, potentiates neuronal tau pathology in multiple preclinical models","volume":"11","author":"Jablonski","year":"2021","journal-title":"Sci. Rep."},{"key":"10.1016\/j.neuron.2026.04.024_bib239","article-title":"Neuronal APOE4 alone is sufficient to drive tau pathology, neurodegeneration, and neuroinflammation in an Alzheimer\u2019s disease mouse model","author":"Blumenfeld","year":"2025","journal-title":"bioRxiv"},{"key":"10.1016\/j.neuron.2026.04.024_bib240","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."},{"key":"10.1016\/j.neuron.2026.04.024_bib241","series-title":"In Neuron-Glia Interaction in Neuroinflammation","first-page":"49","article-title":"Factors from Intact and Damaged Neurons","author":"Mizuno","year":"2013"},{"key":"10.1016\/j.neuron.2026.04.024_bib242","doi-asserted-by":"crossref","first-page":"752","DOI":"10.1016\/j.immuni.2024.03.002","article-title":"DAMPs and DAMP-sensing receptors in inflammation and diseases","volume":"57","author":"Ma","year":"2024","journal-title":"Immunity"},{"key":"10.1016\/j.neuron.2026.04.024_bib243","doi-asserted-by":"crossref","first-page":"87","DOI":"10.1189\/jlb.3MR0416-204R","article-title":"Danger-associated molecular patterns in Alzheimer\u2019s disease","volume":"101","author":"Venegas","year":"2017","journal-title":"J. Leukoc. Biol."},{"key":"10.1016\/j.neuron.2026.04.024_bib244","doi-asserted-by":"crossref","DOI":"10.3389\/fimmu.2021.844315","article-title":"Editorial: DAMPs across the tree of life","volume":"12","author":"Seong","year":"2022","journal-title":"Front. Immunol."},{"key":"10.1016\/j.neuron.2026.04.024_bib245","doi-asserted-by":"crossref","first-page":"54","DOI":"10.1016\/j.bbi.2012.10.014","article-title":"The inflammasome and danger associated molecular patterns (DAMPs) are implicated in cytokine and chemokine responses following stressor exposure","volume":"28","author":"Maslanik","year":"2013","journal-title":"Brain Behav. Immun."},{"key":"10.1016\/j.neuron.2026.04.024_bib246","doi-asserted-by":"crossref","first-page":"152","DOI":"10.1007\/s10495-021-01663-3","article-title":"Release mechanisms of major DAMPs","volume":"26","author":"Murao","year":"2021","journal-title":"Apoptosis"},{"key":"10.1016\/j.neuron.2026.04.024_bib247","doi-asserted-by":"crossref","DOI":"10.1007\/s00401-024-02747-5","article-title":"The necroptosis cell death pathway drives neurodegeneration in Alzheimer\u2019s disease","volume":"147","author":"Balusu","year":"2024","journal-title":"Acta Neuropathol."},{"key":"10.1016\/j.neuron.2026.04.024_bib248","doi-asserted-by":"crossref","first-page":"1434","DOI":"10.1111\/jcmm.17095","article-title":"Roles of receptor-interacting protein kinase 1 in SH-SY5Y cells with beta amyloid-induced neurotoxicity","volume":"26","author":"Chan","year":"2022","journal-title":"J. Cell. Mol. Med."},{"key":"10.1016\/j.neuron.2026.04.024_bib249","doi-asserted-by":"crossref","DOI":"10.1186\/s12974-022-02567-y","article-title":"Hyperphosphorylated tau mediates neuronal death by inducing necroptosis and inflammation in Alzheimer\u2019s disease","volume":"19","author":"Dong","year":"2022","journal-title":"J. Neuroinflamm."},{"key":"10.1016\/j.neuron.2026.04.024_bib250","doi-asserted-by":"crossref","DOI":"10.1186\/s40478-022-01332-9","article-title":"A\u03b2 oligomers trigger necroptosis-mediated neurodegeneration via microglia activation in Alzheimer\u2019s disease","volume":"10","author":"Salvadores","year":"2022","journal-title":"Acta Neuropathol. Commun."},{"key":"10.1016\/j.neuron.2026.04.024_bib251","doi-asserted-by":"crossref","DOI":"10.1186\/s40478-021-01264-w","article-title":"TNF-mediated neuroinflammation is linked to neuronal necroptosis in Alzheimer\u2019s disease hippocampus","volume":"9","author":"Jayaraman","year":"2021","journal-title":"Acta Neuropathol. Commun."},{"key":"10.1016\/j.neuron.2026.04.024_bib252","doi-asserted-by":"crossref","first-page":"1236","DOI":"10.1038\/nn.4608","article-title":"Necroptosis activation in Alzheimer\u2019s disease","volume":"20","author":"Caccamo","year":"2017","journal-title":"Nat. Neurosci."},{"key":"10.1016\/j.neuron.2026.04.024_bib253","doi-asserted-by":"crossref","first-page":"3714","DOI":"10.1111\/bph.13181","article-title":"Amyloid \u03b2: one of three danger-associated molecules that are secondary inducers of the proinflammatory cytokines that mediate Alzheimer\u2019s disease","volume":"172","author":"Clark","year":"2015","journal-title":"Br. J. Pharmacol."},{"key":"10.1016\/j.neuron.2026.04.024_bib254","doi-asserted-by":"crossref","DOI":"10.1016\/j.pneurobio.2021.102212","article-title":"Neuronal ApoE4 stimulates C\/EBP\u03b2 activation, promoting Alzheimer\u2019s disease pathology in a mouse model","volume":"209","author":"Wang","year":"2022","journal-title":"Prog. Neurobiol."},{"key":"10.1016\/j.neuron.2026.04.024_bib255","doi-asserted-by":"crossref","DOI":"10.3390\/cells13020189","article-title":"Age-dependent and A\u03b2-induced dynamic changes in the subcellular localization of HMGB1 in neurons and microglia in the brains of an animal model of Alzheimer\u2019s disease","volume":"13","author":"Seol","year":"2024","journal-title":"Cells"},{"key":"10.1016\/j.neuron.2026.04.024_bib256","doi-asserted-by":"crossref","DOI":"10.3390\/cells9020383","article-title":"Impact of HMGB1, RAGE, and TLR4 in Alzheimer\u2019s Disease (AD): From Risk Factors to Therapeutic Targeting","volume":"9","author":"Paudel","year":"2020","journal-title":"Cells"},{"key":"10.1016\/j.neuron.2026.04.024_bib257","doi-asserted-by":"crossref","DOI":"10.1016\/j.biopha.2023.114541","article-title":"The role of high mobility group box 1 in neuroinflammatory related diseases","volume":"161","author":"Mo","year":"2023","journal-title":"Biomed. Pharmacother."},{"key":"10.1016\/j.neuron.2026.04.024_bib258","doi-asserted-by":"crossref","DOI":"10.1186\/s42494-021-00048-y","article-title":"HMGB1, neuronal excitability and epilepsy","volume":"3","author":"Dai","year":"2021","journal-title":"Acta Epileptologica"},{"key":"10.1016\/j.neuron.2026.04.024_bib259","doi-asserted-by":"crossref","DOI":"10.1038\/srep31895","article-title":"HMGB1, a pathogenic molecule that induces neurite degeneration via TLR4-MARCKS, is a potential therapeutic target for Alzheimer\u2019s disease","volume":"6","author":"Fujita","year":"2016","journal-title":"Sci. Rep."},{"key":"10.1016\/j.neuron.2026.04.024_bib260","article-title":"Microglial amyloid-\u03b21-40 phagocytosis dysfunction is caused by high-mobility group box protein-1: implications for the pathological progression of Alzheimer\u2019s disease","volume":"2012","author":"Takata","year":"2012","journal-title":"Int. J. Alzheimers Dis."},{"key":"10.1016\/j.neuron.2026.04.024_bib261","doi-asserted-by":"crossref","first-page":"225","DOI":"10.1136\/jnnp-2017-315869","article-title":"Interaction between APOE-\u03f54 and HMGB1 is associated with widespread cortical thinning in mild cognitive impairment","volume":"89","author":"Foo","year":"2018","journal-title":"J. Neurol. Neurosurg. Psychiatry"},{"key":"10.1016\/j.neuron.2026.04.024_bib262","doi-asserted-by":"crossref","DOI":"10.1186\/s12974-016-0670-z","article-title":"HMGB1 and thrombin mediate the blood-brain barrier dysfunction acting as biomarkers of neuroinflammation and progression to neurodegeneration in Alzheimer\u2019s disease","volume":"13","author":"Festoff","year":"2016","journal-title":"J. Neuroinflamm."},{"key":"10.1016\/j.neuron.2026.04.024_bib263","doi-asserted-by":"crossref","DOI":"10.1038\/s41467-020-14353-6","article-title":"YAP-dependent necrosis occurs in early stages of Alzheimer\u2019s disease and regulates mouse model pathology","volume":"11","author":"Tanaka","year":"2020","journal-title":"Nat. Commun."},{"key":"10.1016\/j.neuron.2026.04.024_bib264","doi-asserted-by":"crossref","DOI":"10.1186\/1742-2094-5-43","article-title":"Necrotic neurons enhance microglial neurotoxicity through induction of glutaminase by a MyD88-dependent pathway","volume":"5","author":"Pais","year":"2008","journal-title":"J. Neuroinflamm."},{"key":"10.1016\/j.neuron.2026.04.024_bib265","doi-asserted-by":"crossref","first-page":"1821","DOI":"10.1016\/j.neurobiolaging.2006.08.014","article-title":"Inflammatory changes parallel the early stages of Alzheimer disease","volume":"28","author":"Parachikova","year":"2007","journal-title":"Neurobiol. Aging"},{"key":"10.1016\/j.neuron.2026.04.024_bib266","doi-asserted-by":"crossref","DOI":"10.1001\/jamanetworkopen.2018.3597","article-title":"Association of chronic low-grade inflammation with risk of Alzheimer disease in ApoE4 carriers","volume":"1","author":"Tao","year":"2018","journal-title":"JAMA Netw. Open"},{"key":"10.1016\/j.neuron.2026.04.024_bib267","doi-asserted-by":"crossref","first-page":"50","DOI":"10.1016\/j.dadm.2016.12.002","article-title":"The APOE \u03b54 genotype modulates CSF YKL-40 levels and their structural brain correlates in the continuum of Alzheimer\u2019s disease but not those of sTREM2","volume":"6","author":"Gispert","year":"2017","journal-title":"Alzheimers. Dement. (Amst)"},{"key":"10.1016\/j.neuron.2026.04.024_bib268","doi-asserted-by":"crossref","DOI":"10.1001\/jamanetworkopen.2025.8903","article-title":"APOE4, blood neurodegenerative biomarkers, and cognitive decline in community-dwelling older adults","volume":"8","author":"Ng","year":"2025","journal-title":"JAMA Netw. Open"},{"key":"10.1016\/j.neuron.2026.04.024_bib269","doi-asserted-by":"crossref","first-page":"4985","DOI":"10.1038\/s41380-025-03098-7","article-title":"Differential associations of APOE and TREM2 variants with glial fibrillary acidic protein and neurofilament light in plasma of UK Biobank participants support distinct disease mechanisms","volume":"30","author":"Freudenberg-Hua","year":"2025","journal-title":"Mol. Psychiatry"},{"key":"10.1016\/j.neuron.2026.04.024_bib270","doi-asserted-by":"crossref","first-page":"708","DOI":"10.1111\/j.1532-5415.2007.01159.x","article-title":"Systemic markers of inflammation and cognitive decline in old age","volume":"55","author":"Schram","year":"2007","journal-title":"J. Am. Geriatr. Soc."},{"key":"10.1016\/j.neuron.2026.04.024_bib271","doi-asserted-by":"crossref","first-page":"903","DOI":"10.1016\/j.biopsych.2010.08.025","article-title":"YKL-40: A novel prognostic fluid biomarker for preclinical Alzheimer\u2019s disease","volume":"68","author":"Craig-Schapiro","year":"2010","journal-title":"Biol. Psychiatry"},{"key":"10.1016\/j.neuron.2026.04.024_bib272","doi-asserted-by":"crossref","DOI":"10.1038\/s41598-020-59869-5","article-title":"Associations between brain inflammatory profiles and human neuropathology are altered based on apolipoprotein E \u03b54 genotype","volume":"10","author":"Friedberg","year":"2020","journal-title":"Sci. Rep."},{"key":"10.1016\/j.neuron.2026.04.024_bib273","doi-asserted-by":"crossref","first-page":"21","DOI":"10.1016\/j.neuroscience.2012.03.013","article-title":"An apolipoprotein E4 fragment affects matrix metalloproteinase 9, tissue inhibitor of metalloproteinase 1 and cytokine levels in brain cell lines","volume":"210","author":"Dafnis","year":"2012","journal-title":"Neuroscience"},{"key":"10.1016\/j.neuron.2026.04.024_bib274","doi-asserted-by":"crossref","first-page":"56","DOI":"10.1016\/j.neurobiolaging.2020.06.018","article-title":"Apolipoprotein E isoforms differentially regulate matrix metallopeptidase 9 function in Alzheimer\u2019s disease","volume":"95","author":"Ringland","year":"2020","journal-title":"Neurobiol. Aging"},{"key":"10.1016\/j.neuron.2026.04.024_bib275","doi-asserted-by":"crossref","first-page":"67","DOI":"10.1017\/S1041610207005790","article-title":"Profiles of matrix metalloproteinases and their inhibitors in plasma of patients with dementia","volume":"20","author":"Lorenzl","year":"2007","journal-title":"Int. Psychogeriatr."},{"key":"10.1016\/j.neuron.2026.04.024_bib276","doi-asserted-by":"crossref","first-page":"767","DOI":"10.1097\/WNR.0000000000001952","article-title":"Plasma MMP-9\/TIMP-1 ratio serves as a novel potential biomarker in Alzheimer\u2019s disease","volume":"34","author":"Liu","year":"2023","journal-title":"NeuroReport"},{"key":"10.1016\/j.neuron.2026.04.024_bib277","doi-asserted-by":"crossref","DOI":"10.1186\/alzrt44","article-title":"Alterations of matrix metalloproteinases in the healthy elderly with increased risk of prodromal Alzheimer\u2019s disease","volume":"2","author":"Stomrud","year":"2010","journal-title":"Alzheimers Res. Ther."},{"key":"10.1016\/j.neuron.2026.04.024_bib278","doi-asserted-by":"crossref","first-page":"7910","DOI":"10.1523\/JNEUROSCI.16-24-07910.1996","article-title":"Matrix metalloproteinase-9 (MMP-9) is synthesized in neurons of the human hippocampus and is capable of degrading the amyloid-\u03b2 peptide (1\u201340)","volume":"16","author":"Backstrom","year":"1996","journal-title":"J. Neurosci."},{"key":"10.1016\/j.neuron.2026.04.024_bib279","doi-asserted-by":"crossref","first-page":"1309","DOI":"10.1097\/NEN.0b013e3181c22569","article-title":"Increased matrix metalloproteinase 9 activity in mild cognitive impairment","volume":"68","author":"Bruno","year":"2009","journal-title":"J. Neuropathol. Exp. Neurol."},{"key":"10.1016\/j.neuron.2026.04.024_bib280","doi-asserted-by":"crossref","first-page":"331","DOI":"10.14283\/jpad.2022.19","article-title":"Plasma MMP-9 levels as the future risk of conversion to dementia in ApoE4-positive MCI patients: investigation based on the Alzheimer\u2019s disease neuroimaging initiative database","volume":"9","author":"Abe","year":"2022","journal-title":"J. Prev. Alzheimers Dis."},{"key":"10.1016\/j.neuron.2026.04.024_bib281","doi-asserted-by":"crossref","first-page":"391","DOI":"10.3390\/immuno1040027","article-title":"The role of APOE and NF-\u03baB in Alzheimer\u2019s disease","volume":"1","author":"Davies","year":"2021","journal-title":"Immuno"},{"key":"10.1016\/j.neuron.2026.04.024_bib282","doi-asserted-by":"crossref","first-page":"517","DOI":"10.1111\/pcn.13704","article-title":"Synergism of ApoE4 and systemic infectious burden is mediated by the APOE-NLRP3 axis in Alzheimer\u2019s disease","volume":"78","author":"Liu","year":"2024","journal-title":"Psychiatry Clin. Neurosci."},{"key":"10.1016\/j.neuron.2026.04.024_bib283","article-title":"NF-\u03baB signaling in inflammation","volume":"2","author":"Liu","year":"2017","journal-title":"Signal Transduct. Target. Ther."},{"key":"10.1016\/j.neuron.2026.04.024_bib284","doi-asserted-by":"crossref","first-page":"159","DOI":"10.1016\/0006-8993(96)00310-1","article-title":"Enhancement of immunoreactivity for NF-\u03baB in the hippocampal formation and cerebral cortex of Alzheimer\u2019s disease","volume":"735","author":"Terai","year":"1996","journal-title":"Brain Res."},{"key":"10.1016\/j.neuron.2026.04.024_bib285","doi-asserted-by":"crossref","DOI":"10.3390\/ijms252111353","article-title":"NF-\u03baB in Alzheimer\u2019s disease: friend or foe? opposite functions in neurons and glial cells","volume":"25","author":"Kaltschmidt","year":"2024","journal-title":"Int. J. Mol. Sci."},{"key":"10.1016\/j.neuron.2026.04.024_bib286","article-title":"Microglial NF-\u03baB drives tau spreading and toxicity in a mouse model of tauopathy","volume":"13","author":"Wang","year":"2022","journal-title":"Nat. Commun."},{"key":"10.1016\/j.neuron.2026.04.024_bib287","doi-asserted-by":"crossref","DOI":"10.1038\/s41598-024-65248-1","article-title":"The impact of astrocytic NF-\u03baB on healthy and Alzheimer\u2019s disease brains","volume":"14","author":"Jong Huat","year":"2024","journal-title":"Sci. Rep."},{"key":"10.1016\/j.neuron.2026.04.024_bib288","doi-asserted-by":"crossref","DOI":"10.1016\/j.neuropharm.2024.109941","article-title":"NLRP3 inflammasome signalling in Alzheimer\u2019s disease","volume":"252","author":"McManus","year":"2024","journal-title":"Neuropharmacology"},{"key":"10.1016\/j.neuron.2026.04.024_bib289","doi-asserted-by":"crossref","first-page":"1117","DOI":"10.1002\/glia.24160","article-title":"The NLRP3 inflammasome modulates tau pathology and neurodegeneration in a tauopathy model","volume":"70","author":"Stancu","year":"2022","journal-title":"Glia"},{"key":"10.1016\/j.neuron.2026.04.024_bib290","doi-asserted-by":"crossref","first-page":"1143","DOI":"10.3233\/JAD-170634","article-title":"Co-localization of glia maturation factor with NLRP3 inflammasome and autophagosome markers in human Alzheimer\u2019s disease brain","volume":"60","author":"Ahmed","year":"2017","journal-title":"J. Alzheimers Dis."},{"key":"10.1016\/j.neuron.2026.04.024_bib291","doi-asserted-by":"crossref","DOI":"10.1186\/s13024-016-0088-1","article-title":"The NLRP3 and NLRP1 inflammasomes are activated in Alzheimer\u2019s disease","volume":"11","author":"Saresella","year":"2016","journal-title":"Mol. Neurodegener."},{"key":"10.1016\/j.neuron.2026.04.024_bib292","doi-asserted-by":"crossref","DOI":"10.1111\/nan.12756","article-title":"Expression pattern of perilipins in human brain during aging and in Alzheimer\u2019s disease","volume":"48","author":"Conte","year":"2022","journal-title":"Neuropathol. Appl. Neurobiol."},{"key":"10.1016\/j.neuron.2026.04.024_bib293","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"},{"key":"10.1016\/j.neuron.2026.04.024_bib294","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."},{"key":"10.1016\/j.neuron.2026.04.024_bib295","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."},{"key":"10.1016\/j.neuron.2026.04.024_bib296","doi-asserted-by":"crossref","first-page":"128","DOI":"10.1016\/j.cmet.2020.05.003","article-title":"Toll-like receptors induce signal-specific reprogramming of the macrophage lipidome","volume":"32","author":"Hsieh","year":"2020","journal-title":"Cell Metab."},{"key":"10.1016\/j.neuron.2026.04.024_bib297","doi-asserted-by":"crossref","first-page":"3001","DOI":"10.1074\/jbc.M113.524587","article-title":"Toll-like receptor agonists promote prolonged triglyceride storage in macrophages","volume":"289","author":"Huang","year":"2014","journal-title":"J. Biol. Chem."},{"key":"10.1016\/j.neuron.2026.04.024_bib298","doi-asserted-by":"crossref","first-page":"2690","DOI":"10.1093\/hmg\/ddx155","article-title":"APOE \u03b54\/\u03b54 diminishes neurotrophic function of human iPSC-derived astrocytes","volume":"26","author":"Zhao","year":"2017","journal-title":"Hum. Mol. Genet."},{"key":"10.1016\/j.neuron.2026.04.024_bib299","doi-asserted-by":"crossref","first-page":"110","DOI":"10.1016\/j.stemcr.2021.11.007","article-title":"APOE2, E3, and E4 differentially modulate cellular homeostasis, cholesterol metabolism, and inflammatory response in isogenic iPSC-derived astrocytes","volume":"17","author":"de Leeuw","year":"2022","journal-title":"Stem Cell Rep."},{"key":"10.1016\/j.neuron.2026.04.024_bib300","doi-asserted-by":"crossref","DOI":"10.1177\/17590914221144549","article-title":"Sex and APOE genotype alter the basal and induced inflammatory states of primary astrocytes from humanized targeted replacement mice","volume":"15","author":"Mhatre-Winters","year":"2023","journal-title":"ASN Neuro"},{"key":"10.1016\/j.neuron.2026.04.024_bib301","doi-asserted-by":"crossref","first-page":"17536","DOI":"10.1074\/jbc.M111.225532","article-title":"Apolipoprotein E regulates the integrity of tight junctions in an isoform-dependent manner in an in vitro blood-brain barrier model","volume":"286","author":"Nishitsuji","year":"2011","journal-title":"J. Biol. Chem."},{"key":"10.1016\/j.neuron.2026.04.024_bib302","doi-asserted-by":"crossref","first-page":"3582","DOI":"10.1093\/brain\/awab478","article-title":"APOE4 derived from astrocytes leads to blood\u2013brain barrier impairment","volume":"145","author":"Jackson","year":"2022","journal-title":"Brain"},{"key":"10.1016\/j.neuron.2026.04.024_bib303","doi-asserted-by":"crossref","DOI":"10.1186\/s13024-023-00610-x","article-title":"Astrocytic APOE4 removal confers cerebrovascular protection despite increased cerebral amyloid angiopathy","volume":"18","author":"Xiong","year":"2023","journal-title":"Mol. Neurodegener."},{"key":"10.1016\/j.neuron.2026.04.024_bib304","doi-asserted-by":"crossref","first-page":"4386","DOI":"10.1016\/j.cell.2023.08.037","article-title":"Human microglial state dynamics in Alzheimer\u2019s disease progression","volume":"186","author":"Sun","year":"2023","journal-title":"Cell"},{"key":"10.1016\/j.neuron.2026.04.024_bib305","doi-asserted-by":"crossref","DOI":"10.1186\/s13024-018-0301-5","article-title":"Early increase of CSF sTREM2 in Alzheimer\u2019s disease is associated with tau related-neurodegeneration but not with amyloid-\u03b2 pathology","volume":"14","author":"Su\u00e1rez-Calvet","year":"2019","journal-title":"Mol. Neurodegener."},{"key":"10.1016\/j.neuron.2026.04.024_bib306","doi-asserted-by":"crossref","DOI":"10.15252\/emmm.202216987","article-title":"sTREM2 is associated with amyloid-related p-tau increases and glucose hypermetabolism in Alzheimer\u2019s disease","volume":"15","author":"Biel","year":"2023","journal-title":"EMBO Mol. Med."},{"key":"10.1016\/j.neuron.2026.04.024_bib307","doi-asserted-by":"crossref","first-page":"1854","DOI":"10.1038\/s41590-023-01640-9","article-title":"Cell-autonomous effects of APOE4 in restricting microglial response in brain homeostasis and Alzheimer\u2019s disease","volume":"24","author":"Liu","year":"2023","journal-title":"Nat. Immunol."},{"key":"10.1016\/j.neuron.2026.04.024_bib308","doi-asserted-by":"crossref","first-page":"1839","DOI":"10.1038\/s41590-023-01627-6","article-title":"APOE4 impairs the microglial response in Alzheimer\u2019s disease by inducing TGF\u03b2-mediated checkpoints","volume":"24","author":"Yin","year":"2023","journal-title":"Nat. Immunol."},{"key":"10.1016\/j.neuron.2026.04.024_bib309","doi-asserted-by":"crossref","DOI":"10.1016\/j.celrep.2020.107962","article-title":"In vivo chimeric Alzheimer\u2019s disease modeling of apolipoprotein E4 toxicity in human neurons","volume":"32","author":"Najm","year":"2020","journal-title":"Cell Rep."},{"key":"10.1016\/j.neuron.2026.04.024_bib310","doi-asserted-by":"crossref","first-page":"717","DOI":"10.1093\/jnen\/nlac054","article-title":"Apolipoprotein E \u03b54 mediates myelin breakdown by targeting oligodendrocytes in sporadic Alzheimer disease","volume":"81","author":"Cheng","year":"2022","journal-title":"J. Neuropathol. Exp. Neurol."},{"key":"10.1016\/j.neuron.2026.04.024_bib311","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"},{"key":"10.1016\/j.neuron.2026.04.024_bib312","doi-asserted-by":"crossref","first-page":"709","DOI":"10.1007\/s00401-016-1547-z","article-title":"The role of APOE in cerebrovascular dysfunction","volume":"131","author":"Tai","year":"2016","journal-title":"Acta Neuropathol."},{"key":"10.1016\/j.neuron.2026.04.024_bib313","doi-asserted-by":"crossref","first-page":"216","DOI":"10.1038\/jcbfm.2015.44","article-title":"Accelerated pericyte degeneration and blood\u2013brain barrier breakdown in apolipoprotein E4 carriers with Alzheimer\u2019s disease","volume":"36","author":"Halliday","year":"2016","journal-title":"J. Cereb. Blood Flow Metab."},{"key":"10.1016\/j.neuron.2026.04.024_bib314","doi-asserted-by":"crossref","first-page":"71","DOI":"10.1038\/s41586-020-2247-3","article-title":"APOE4 leads to blood\u2013brain barrier dysfunction predicting cognitive decline","volume":"581","author":"Montagne","year":"2020","journal-title":"Nature"},{"key":"10.1016\/j.neuron.2026.04.024_bib315","doi-asserted-by":"crossref","first-page":"885","DOI":"10.1038\/s41586-021-04369-3","article-title":"A human brain vascular atlas reveals diverse mediators of Alzheimer\u2019s risk","volume":"603","author":"Yang","year":"2022","journal-title":"Nature"},{"key":"10.1016\/j.neuron.2026.04.024_bib316","doi-asserted-by":"crossref","first-page":"e195","DOI":"10.1161\/ATVBAHA.118.312261","article-title":"Apolipoprotein E4 expression causes gain of toxic function in isogenic human induced pluripotent stem cell-derived endothelial cells","volume":"39","author":"Rieker","year":"2019","journal-title":"Arterioscler. Thromb. Vasc. Biol."},{"key":"10.1016\/j.neuron.2026.04.024_bib317","doi-asserted-by":"crossref","first-page":"952","DOI":"10.1038\/s41591-020-0886-4","article-title":"Reconstruction of the human blood\u2013brain barrier in vitro reveals a pathogenic mechanism of APOE4 in pericytes","volume":"26","author":"Blanchard","year":"2020","journal-title":"Nat. Med."},{"key":"10.1016\/j.neuron.2026.04.024_bib318","doi-asserted-by":"crossref","first-page":"3621","DOI":"10.1523\/JNEUROSCI.4213-04.2005","article-title":"Apolipoprotein E genotype regulates amyloid-\u03b2 cytotoxicity","volume":"25","author":"Wilhelmus","year":"2005","journal-title":"J. Neurosci."},{"key":"10.1016\/j.neuron.2026.04.024_bib319","doi-asserted-by":"crossref","first-page":"86","DOI":"10.1038\/jcbfm.2014.172","article-title":"Human apolipoprotein E \u03b54 expression impairs cerebral vascularization and blood-brain barrier function in mice","volume":"35","author":"Alata","year":"2015","journal-title":"J. Cereb. Blood Flow Metab."},{"key":"10.1016\/j.neuron.2026.04.024_bib320","doi-asserted-by":"crossref","DOI":"10.1186\/s40035-025-00512-6","article-title":"Transplantation of hiPSC-derived pericytes rescues Alzheimer\u2019s disease phenotypes in APOE4\/4 mice through IGF2-rich apoptotic vesicles","volume":"14","author":"Xiong","year":"2025","journal-title":"Transl. Neurodegener."},{"key":"10.1016\/j.neuron.2026.04.024_bib321","doi-asserted-by":"crossref","first-page":"438","DOI":"10.1016\/j.neuron.2020.11.019","article-title":"Vascular ApoE4 impairs behavior by modulating gliovascular function","volume":"109","author":"Yamazaki","year":"2021","journal-title":"Neuron"},{"key":"10.1016\/j.neuron.2026.04.024_bib322","doi-asserted-by":"crossref","first-page":"399","DOI":"10.1111\/jnc.15238","volume":"156","author":"Gulyaeva","year":"2021","journal-title":"J. Neurochem."},{"key":"10.1016\/j.neuron.2026.04.024_bib323","doi-asserted-by":"crossref","DOI":"10.1016\/j.neuropharm.2020.108352","article-title":"Efficacy of acetylcholinesterase inhibitors in Alzheimer\u2019s disease","volume":"190","author":"Marucci","year":"2021","journal-title":"Neuropharmacology"},{"key":"10.1016\/j.neuron.2026.04.024_bib324","series-title":"Diagnosis and Management in Dementia","first-page":"573","article-title":"Dementia and usage of N-methyl-d-aspartate receptor antagonists","author":"Glynn-Servedio","year":"2020"},{"key":"10.1016\/j.neuron.2026.04.024_bib325","doi-asserted-by":"crossref","first-page":"399","DOI":"10.1038\/s41582-018-0013-z","article-title":"Tau-targeting therapies for Alzheimer disease","volume":"14","author":"Congdon","year":"2018","journal-title":"Nat. Rev. Neurol."},{"key":"10.1016\/j.neuron.2026.04.024_bib326","article-title":"Amyloid \u03b2-based therapy for Alzheimer\u2019s disease: challenges, successes and future","volume":"8","author":"Zhang","year":"2023","journal-title":"Signal Transduct. Target. Ther."},{"key":"10.1016\/j.neuron.2026.04.024_bib327","doi-asserted-by":"crossref","DOI":"10.1186\/s40035-025-00465-w","article-title":"Second-generation anti-amyloid monoclonal antibodies for Alzheimer\u2019s disease: current landscape and future perspectives","volume":"14","author":"Kim","year":"2025","journal-title":"Transl. Neurodegener."},{"key":"10.1016\/j.neuron.2026.04.024_bib328","doi-asserted-by":"crossref","first-page":"117","DOI":"10.4103\/1673-5374.340409","article-title":"Initial failures of anti-tau antibodies in Alzheimer\u2019s disease are reminiscent of the amyloid-\u03b2 story","volume":"18","author":"Imbimbo","year":"2023","journal-title":"Neural Regen. Res."},{"key":"10.1016\/j.neuron.2026.04.024_bib329","doi-asserted-by":"crossref","first-page":"461","DOI":"10.1001\/jamaneurol.2025.0065","article-title":"Amyloid-related imaging abnormalities with donanemab in early symptomatic Alzheimer disease: secondary analysis of the TRAILBLAZER-ALZ and ALZ 2 randomized clinical trials","volume":"82","author":"Zimmer","year":"2025","journal-title":"JAMA Neurol."},{"key":"10.1016\/j.neuron.2026.04.024_bib330","doi-asserted-by":"crossref","DOI":"10.1212\/WNL.0000000000213483","article-title":"Incidence of amyloid-related imaging abnormalities in phase iii clinical trials of anti-amyloid-\u03b2 immunotherapy: an updated meta-analysis","volume":"104","author":"Jeong","year":"2025","journal-title":"Neurology"},{"key":"10.1016\/j.neuron.2026.04.024_bib331","doi-asserted-by":"crossref","first-page":"773","DOI":"10.1007\/s40263-016-0361-4","article-title":"Apolipoprotein E as a therapeutic target in Alzheimer\u2019s disease: a review of basic research and clinical evidence","volume":"30","author":"Yamazaki","year":"2016","journal-title":"CNS Drugs"},{"key":"10.1016\/j.neuron.2026.04.024_bib332","doi-asserted-by":"crossref","first-page":"1013","DOI":"10.1016\/j.neuron.2017.11.014","article-title":"Age-dependent effects of apoE reduction using antisense oligonucleotides in a model of \u03b2-amyloidosis","volume":"96","author":"Huynh","year":"2017","journal-title":"Neuron"},{"key":"10.1016\/j.neuron.2026.04.024_bib333","article-title":"Neuronal APOE4 reduction with an APOE-I3-targeting ASO protects against neurodegeneration and neuroinflammation in an Alzheimer\u2019s disease mouse model","author":"Yip","year":"2025","journal-title":"bioRxiv"},{"key":"10.1016\/j.neuron.2026.04.024_bib334","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\u2019s disease","volume":"14","author":"Rohn","year":"2013","journal-title":"Int. J. Mol. Sci."},{"key":"10.1016\/j.neuron.2026.04.024_bib335","doi-asserted-by":"crossref","DOI":"10.1155\/2013\/620793","article-title":"Novel natural structure corrector of ApoE4 for checking Alzheimer\u2019s disease: benefits from high throughput screening and molecular dynamics simulations","volume":"2013","author":"Goyal","year":"2013","journal-title":"BioMed Res. Int."},{"key":"10.1016\/j.neuron.2026.04.024_bib336","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","year":"2012","journal-title":"J. Biol. Chem."},{"key":"10.1016\/j.neuron.2026.04.024_bib337","doi-asserted-by":"crossref","first-page":"4120","DOI":"10.1021\/acs.jmedchem.9b00178","article-title":"Fragment-based discovery of an apolipoprotein E4 (apoE4) stabilizer","volume":"62","author":"Petros","year":"2019","journal-title":"J. Med. Chem."},{"key":"10.1016\/j.neuron.2026.04.024_bib338","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"},{"key":"10.1016\/j.neuron.2026.04.024_bib339","doi-asserted-by":"crossref","first-page":"9506","DOI":"10.1523\/JNEUROSCI.0693-14.2014","article-title":"Inhibitory interneuron progenitor transplantation restores normal learning and memory in ApoE4 knock-in mice without or with A\u03b2 accumulation","volume":"34","author":"Tong","year":"2014","journal-title":"J. Neurosci."},{"key":"10.1016\/j.neuron.2026.04.024_bib340","doi-asserted-by":"crossref","first-page":"649","DOI":"10.1111\/jnc.14345","article-title":"The GABAergic system as a therapeutic target for Alzheimer\u2019s disease","volume":"146","author":"Calvo-Flores Guzm\u00e1n","year":"2018","journal-title":"J. Neurochem."},{"key":"10.1016\/j.neuron.2026.04.024_bib341","doi-asserted-by":"crossref","DOI":"10.3389\/fncel.2025.1675003","article-title":"Brain-derived neurotrophic factor prevents LPS-induced dysregulation of GABAergic interneuron markers in mouse hippocampus","volume":"19","author":"Rezaei","year":"2025","journal-title":"Front. Cell. Neurosci."},{"key":"10.1016\/j.neuron.2026.04.024_bib342","doi-asserted-by":"crossref","DOI":"10.3389\/fnagi.2024.1354164","article-title":"Human stem cell transplantation models of Alzheimer\u2019s disease","volume":"16","author":"Ifediora","year":"2024","journal-title":"Front. Aging Neurosci."},{"key":"10.1016\/j.neuron.2026.04.024_bib343","doi-asserted-by":"crossref","first-page":"220","DOI":"10.1016\/j.expneurol.2015.11.003","article-title":"Anti-high mobility group box 1 antibody exerts neuroprotection in a rat model of Parkinson\u2019s disease","volume":"275","author":"Sasaki","year":"2016","journal-title":"Exp. Neurol."},{"key":"10.1016\/j.neuron.2026.04.024_bib344","doi-asserted-by":"crossref","first-page":"308","DOI":"10.1016\/j.bbi.2017.02.002","article-title":"Therapeutic potential of an anti-high mobility group box-1 monoclonal antibody in epilepsy","volume":"64","author":"Zhao","year":"2017","journal-title":"Brain Behav. Immun."},{"key":"10.1016\/j.neuron.2026.04.024_bib345","article-title":"Anti-high mobility group box-1 (HMGB1) antibody inhibits hemorrhage-induced brain injury and improved neurological deficits in rats","volume":"7","author":"Wang","year":"2017","journal-title":"Sci. Rep."},{"key":"10.1016\/j.neuron.2026.04.024_bib346","doi-asserted-by":"crossref","first-page":"94","DOI":"10.1016\/j.jphs.2019.04.006","article-title":"Anti-HMGB1 monoclonal antibody therapy for a wide range of CNS and PNS diseases","volume":"140","author":"Nishibori","year":"2019","journal-title":"J. Pharmacol. Sci."},{"key":"10.1016\/j.neuron.2026.04.024_bib347","doi-asserted-by":"crossref","first-page":"5516","DOI":"10.1016\/j.cell.2025.06.035","article-title":"Cell-type-directed network-correcting combination therapy for Alzheimer\u2019s disease","volume":"188","author":"Li","year":"2025","journal-title":"Cell"},{"key":"10.1016\/j.neuron.2026.04.024_bib348","doi-asserted-by":"crossref","first-page":"414","DOI":"10.1038\/s41588-019-0358-2","article-title":"Genetic meta-analysis of diagnosed Alzheimer\u2019s disease identifies new risk loci and implicates A\u03b2, tau, immunity and lipid processing","volume":"51","author":"Kunkle","year":"2019","journal-title":"Nat. Genet."},{"key":"10.1016\/j.neuron.2026.04.024_bib349","doi-asserted-by":"crossref","first-page":"1241","DOI":"10.1038\/s41591-024-02923-w","article-title":"APOE4 homozygosity is a new genetic form of Alzheimer\u2019s disease","volume":"30","author":"Xu","year":"2024","journal-title":"Nat. Med."},{"key":"10.1016\/j.neuron.2026.04.024_bib350","doi-asserted-by":"crossref","DOI":"10.1038\/s44400-025-00045-9","article-title":"The proportion of Alzheimer's disease attributable to apolipoprotein E","volume":"2","author":"Williams","year":"2026","journal-title":"NPJ Dement."}],"container-title":["Neuron"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S0896627326003193?httpAccept=text\/xml","content-type":"text\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S0896627326003193?httpAccept=text\/plain","content-type":"text\/plain","content-version":"vor","intended-application":"text-mining"}],"deposited":{"date-parts":[[2026,8,19]],"date-time":"2026-08-19T15:22:56Z","timestamp":1787152976000},"score":1,"resource":{"primary":{"URL":"https:\/\/linkinghub.elsevier.com\/retrieve\/pii\/S0896627326003193"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,8]]},"references-count":350,"journal-issue":{"issue":"16","published-print":{"date-parts":[[2026,8]]}},"alternative-id":["S0896627326003193"],"URL":"https:\/\/doi.org\/10.1016\/j.neuron.2026.04.024","relation":{},"ISSN":["0896-6273"],"issn-type":[{"value":"0896-6273","type":"print"}],"subject":[],"published":{"date-parts":[[2026,8]]},"assertion":[{"value":"Elsevier","name":"publisher","label":"This article is maintained by"},{"value":"Cell-type-specific APOE4 cascade across the Alzheimer\u2019s disease continuum","name":"articletitle","label":"Article Title"},{"value":"Neuron","name":"journaltitle","label":"Journal Title"},{"value":"https:\/\/doi.org\/10.1016\/j.neuron.2026.04.024","name":"articlelink","label":"CrossRef DOI link to publisher maintained version"},{"value":"article","name":"content_type","label":"Content Type"},{"value":"\u00a9 2026 The Authors. Published by Elsevier Inc.","name":"copyright","label":"Copyright"}]}}