{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,8]],"date-time":"2026-08-08T17:43:23Z","timestamp":1786211003059,"version":"build-2736575974"},"reference-count":62,"publisher":"Springer Science and Business Media LLC","license":[{"start":{"date-parts":[[2026,8,8]],"date-time":"2026-08-08T00:00:00Z","timestamp":1786147200000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.springernature.com\/gp\/researchers\/text-and-data-mining"},{"start":{"date-parts":[[2026,8,8]],"date-time":"2026-08-08T00:00:00Z","timestamp":1786147200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/www.springernature.com\/gp\/researchers\/text-and-data-mining"}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Neurosci. Bull."],"DOI":"10.1007\/s12264-026-01693-4","type":"journal-article","created":{"date-parts":[[2026,8,8]],"date-time":"2026-08-08T15:17:09Z","timestamp":1786202229000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["An ApoE-Associated Low-Inflammatory Microglial State Emerges After Inflammatory Challenge in Alzheimer\u2019s Disease Mice"],"prefix":"10.1007","author":[{"given":"Wenwen","family":"Cai","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaoli","family":"Pan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ting","family":"Qian","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shiwen","family":"Yu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ruoqi","family":"Zhao","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cuiqing","family":"Zhu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shaoming","family":"Sang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7870-3441","authenticated-orcid":false,"given":"Chunjiu","family":"Zhong","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2026,8,8]]},"reference":[{"key":"1693_CR1","doi-asserted-by":"publisher","first-page":"329","DOI":"10.1056\/NEJMra0909142","volume":"362","author":"HW Querfurth","year":"2010","unstructured":"Querfurth HW, LaFerla FM. Alzheimer\u2019s disease. N Engl J Med 2010, 362: 329\u2013344.","journal-title":"N Engl J Med"},{"key":"1693_CR2","doi-asserted-by":"publisher","first-page":"603","DOI":"10.1016\/j.cell.2015.12.056","volume":"164","author":"B De Strooper","year":"2016","unstructured":"De Strooper B, Karran E. The cellular phase of Alzheimer\u2019s disease. Cell 2016, 164: 603\u2013615.","journal-title":"Cell"},{"key":"1693_CR3","doi-asserted-by":"publisher","first-page":"321","DOI":"10.1038\/s41577-024-01104-7","volume":"25","author":"MT Heneka","year":"2025","unstructured":"Heneka MT, van der Flier WM, Jessen F, Hoozemanns J, Thal DR, Boche D. Neuroinflammation in Alzheimer disease. Nat Rev Immunol 2025, 25: 321\u2013352.","journal-title":"Nat Rev Immunol"},{"key":"1693_CR4","doi-asserted-by":"publisher","first-page":"768","DOI":"10.1212\/WNL.0b013e3181b6bb95","volume":"73","author":"C Holmes","year":"2009","unstructured":"Holmes C, Cunningham C, Zotova E, Woolford J, Dean C, Kerr S, et al. Systemic inflammation and disease progression in Alzheimer disease. Neurology 2009, 73: 768\u2013774.","journal-title":"Neurology"},{"key":"1693_CR5","doi-asserted-by":"publisher","first-page":"212","DOI":"10.1212\/WNL.0b013e318225ae07","volume":"77","author":"C Holmes","year":"2011","unstructured":"Holmes C, Cunningham C, Zotova E, Culliford D, Perry VH. Proinflammatory cytokines, sickness behavior, and Alzheimer disease. Neurology 2011, 77: 212\u2013218.","journal-title":"Neurology"},{"key":"1693_CR6","doi-asserted-by":"publisher","first-page":"581","DOI":"10.1016\/S0361-9230(01)00730-4","volume":"56","author":"LM Sly","year":"2001","unstructured":"Sly LM, Krzesicki RF, Brashler JR, Buhl AE, McKinley DD, Carter DB, et al. Endogenous brain cytokine mRNA and inflammatory responses to lipopolysaccharide are elevated in the Tg2576 transgenic mouse model of Alzheimer\u2019s disease. Brain Res Bull 2001, 56: 581\u2013588.","journal-title":"Brain Res Bull"},{"key":"1693_CR7","doi-asserted-by":"publisher","first-page":"29","DOI":"10.1385\/NMM:2:1:29","volume":"2","author":"J Lee","year":"2002","unstructured":"Lee J, Chan SL, Mattson MP. Adverse effect of a presenilin-1 mutation in microglia results in enhanced nitric oxide and inflammatory cytokine responses to immune challenge in the brain. NeuroMolecular Med 2002, 2: 29\u201345.","journal-title":"NeuroMolecular Med"},{"key":"1693_CR8","doi-asserted-by":"publisher","first-page":"217","DOI":"10.1038\/nrneurol.2014.38","volume":"10","author":"VH Perry","year":"2014","unstructured":"Perry VH, Holmes C. Microglial priming in neurodegenerative disease. Nat Rev Neurol 2014, 10: 217\u2013224.","journal-title":"Nat Rev Neurol"},{"key":"1693_CR9","doi-asserted-by":"publisher","first-page":"566","DOI":"10.1016\/j.immuni.2017.08.008","volume":"47","author":"S Krasemann","year":"2017","unstructured":"Krasemann S, Madore C, Cialic R, Baufeld C, Calcagno N, El Fatimy R, et al. The TREM2-APOE pathway drives the transcriptional phenotype of dysfunctional microglia in neurodegenerative diseases. Immunity 2017, 47: 566-581.e9.","journal-title":"Immunity"},{"key":"1693_CR10","doi-asserted-by":"publisher","first-page":"1276","DOI":"10.1016\/j.cell.2017.05.018","volume":"169","author":"H Keren-Shaul","year":"2017","unstructured":"Keren-Shaul H, Spinrad A, Weiner A, Matcovitch-Natan O, Dvir-Szternfeld R, Ulland TK et al (2017) A unique microglia type associated with restricting development of Alzheimer\u2019s disease. Cell 169:1276\u20131290.e17","journal-title":"Cell"},{"key":"1693_CR11","doi-asserted-by":"publisher","first-page":"1052","DOI":"10.1016\/j.immuni.2025.04.009","volume":"58","author":"C Depp","year":"2025","unstructured":"Depp C, Doman JL, Hingerl M, Xia J, Stevens B. Microglia transcriptional states and their functional significance: Context drives diversity. Immunity 2025, 58: 1052\u20131067.","journal-title":"Immunity"},{"key":"1693_CR12","doi-asserted-by":"publisher","first-page":"2808","DOI":"10.1007\/s12035-023-03736-7","volume":"61","author":"W Tsering","year":"2024","unstructured":"Tsering W, Prokop S. Neuritic plaques\u2014Gateways to understanding Alzheimer\u2019s disease. Mol Neurobiol 2024, 61: 2808\u20132821.","journal-title":"Mol Neurobiol"},{"key":"1693_CR13","doi-asserted-by":"publisher","first-page":"133","DOI":"10.3109\/10520290903389445","volume":"85","author":"M D\u2019Andrea","year":"2010","unstructured":"D\u2019Andrea M, Nagele R. Morphologically distinct types of amyloid plaques point the way to a better understanding of Alzheimer\u2019s disease pathogenesis. Biotech Histochem 2010, 85: 133\u2013147.","journal-title":"Biotech Histochem"},{"key":"1693_CR14","doi-asserted-by":"publisher","first-page":"1125","DOI":"10.1007\/s12264-022-00927-5","volume":"38","author":"F Liu","year":"2022","unstructured":"Liu F, Sun J, Wang X, Jin S, Sun F, Wang T, et al. Focal-type, but not diffuse-type, amyloid beta plaques are correlated with Alzheimer\u2019s neuropathology, cognitive dysfunction, and neuroinflammation in the human hippocampus. Neurosci Bull 2022, 38: 1125\u20131138.","journal-title":"Neurosci Bull"},{"key":"1693_CR15","doi-asserted-by":"publisher","first-page":"66","DOI":"10.1111\/j.1750-3639.2008.00244.x","volume":"20","author":"PT Nelson","year":"2010","unstructured":"Nelson PT, Abner EL, Schmitt FA, Kryscio RJ, Jicha GA, Smith CD, et al. Modeling the association between 43 different clinical and pathological variables and the severity of cognitive impairment in a large autopsy cohort of elderly persons. Brain Pathol 2010, 20: 66\u201379.","journal-title":"Brain Pathol"},{"key":"1693_CR16","doi-asserted-by":"publisher","first-page":"328","DOI":"10.1038\/s41586-022-05491-6","volume":"612","author":"P Yuan","year":"2022","unstructured":"Yuan P, Zhang M, Tong L, Morse TM, McDougal RA, Ding H, et al. PLD3 affects axonal spheroids and network defects in Alzheimer\u2019s disease. Nature 2022, 612: 328\u2013337.","journal-title":"Nature"},{"key":"1693_CR17","doi-asserted-by":"publisher","first-page":"1116","DOI":"10.1038\/s41419-018-1155-z","volume":"9","author":"V Shacham-Silverberg","year":"2018","unstructured":"Shacham-Silverberg V, Sar Shalom H, Goldner R, Golan-Vaishenker Y, Gurwicz N, Gokhman I, et al. Phosphatidylserine is a marker for axonal debris engulfment but its exposure can be decoupled from degeneration. Cell Death Dis 2018, 9: 1116.","journal-title":"Cell Death Dis"},{"key":"1693_CR18","doi-asserted-by":"publisher","first-page":"569","DOI":"10.1007\/BF00687883","volume":"77","author":"S Haga","year":"1989","unstructured":"Haga S, Akai K, Ishii T. Demonstration of microglial cells in and around senile (neuritic) plaques in the Alzheimer brain. An immunohistochemical study using a novel monoclonal antibody. Acta Neuropathol 1989, 77: 569\u2013575.","journal-title":"Acta Neuropathol"},{"key":"1693_CR19","doi-asserted-by":"publisher","first-page":"242","DOI":"10.1007\/BF00305864","volume":"81","author":"T Ohgami","year":"1991","unstructured":"Ohgami T, Kitamoto T, Shin RW, Kaneko Y, Ogomori K, Tateishi J. Increased senile plaques without microglia in Alzheimer\u2019s disease. Acta Neuropathol 1991, 81: 242\u2013247.","journal-title":"Acta Neuropathol"},{"key":"1693_CR20","doi-asserted-by":"publisher","first-page":"2127","DOI":"10.1016\/j.devcel.2022.07.015","volume":"57","author":"DA Menassa","year":"2022","unstructured":"Menassa DA, Muntslag TAO, Martin-Esteban\u00e9 M, Barry-Carroll L, Chapman MA, Adorjan I et al (2022) The spatiotemporal dynamics of microglia across the human lifespan. Dev Cell 57:2127\u20132139.e6","journal-title":"Dev Cell"},{"key":"1693_CR21","doi-asserted-by":"publisher","first-page":"619","DOI":"10.1146\/annurev-physiol-022516-034406","volume":"79","author":"SA Wolf","year":"2017","unstructured":"Wolf SA, Boddeke HWGM, Kettenmann H. Microglia in physiology and disease. Annu Rev Physiol 2017, 79: 619\u2013643.","journal-title":"Annu Rev Physiol"},{"key":"1693_CR22","doi-asserted-by":"publisher","first-page":"553","DOI":"10.1007\/s12264-022-01010-9","volume":"39","author":"K Cao","year":"2023","unstructured":"Cao K, Hu Y, Gao Z. Sense to tune: Engaging microglia with dynamic neuronal activity. Neurosci Bull 2023, 39: 553\u2013556.","journal-title":"Neurosci Bull"},{"key":"1693_CR23","doi-asserted-by":"publisher","first-page":"102448","DOI":"10.1016\/j.redox.2022.102448","volume":"56","author":"S Wendt","year":"2022","unstructured":"Wendt S, Johnson S, Weilinger NL, Groten C, Sorrentino S, Frew J, et al. Simultaneous imaging of redox states in dystrophic neurites and microglia at A\u03b2 plaques indicate lysosome accumulation not microglia correlate with increased oxidative stress. Redox Biol 2022, 56: 102448.","journal-title":"Redox Biol"},{"key":"1693_CR24","doi-asserted-by":"publisher","first-page":"87","DOI":"10.1186\/s12974-019-1473-9","volume":"16","author":"H El Hajj","year":"2019","unstructured":"El Hajj H, Savage JC, Bisht K, Parent M, Valli\u00e8res L, Rivest S, et al. Ultrastructural evidence of microglial heterogeneity in Alzheimer\u2019s disease amyloid pathology. J Neuroinflammation 2019, 16: 87.","journal-title":"J Neuroinflammation"},{"key":"1693_CR25","doi-asserted-by":"publisher","first-page":"105072","DOI":"10.1016\/j.nbd.2020.105072","volume":"145","author":"VE von Saucken","year":"2020","unstructured":"von Saucken VE, Jay TR, Landreth GE. The effect of amyloid on microglia-neuron interactions before plaque onset occurs independently of TREM2 in a mouse model of Alzheimer\u2019s disease. Neurobiol Dis 2020, 145: 105072.","journal-title":"Neurobiol Dis"},{"key":"1693_CR26","doi-asserted-by":"publisher","first-page":"3015","DOI":"10.1038\/s41467-021-23111-1","volume":"12","author":"A Grubman","year":"2021","unstructured":"Grubman A, Choo XY, Chew G, Ouyang JF, Sun G, Croft NP, et al. Transcriptional signature in microglia associated with A\u03b2 plaque phagocytosis. Nat Commun 2021, 12: 3015.","journal-title":"Nat Commun"},{"key":"1693_CR27","doi-asserted-by":"publisher","first-page":"493","DOI":"10.1016\/j.cmet.2019.06.005","volume":"30","author":"SH Baik","year":"2019","unstructured":"Baik SH, Kang S, Lee W, Choi H, Chung S, Kim JI, et al. A breakdown in metabolic reprogramming causes microglia dysfunction in Alzheimer\u2019s disease. Cell Metab 2019, 30: 493-507.e6.","journal-title":"Cell Metab"},{"key":"1693_CR28","doi-asserted-by":"publisher","first-page":"183","DOI":"10.1016\/j.bbi.2017.10.017","volume":"68","author":"R Holland","year":"2018","unstructured":"Holland R, McIntosh AL, Finucane OM, Mela V, Rubio-Araiz A, Timmons G, et al. Inflammatory microglia are glycolytic and iron retentive and typify the microglia in APP\/PS1 mice. Brain Behav Immun 2018, 68: 183\u2013196.","journal-title":"Brain Behav Immun"},{"key":"1693_CR29","doi-asserted-by":"publisher","first-page":"606","DOI":"10.1111\/bpa.12704","volume":"29","author":"A McIntosh","year":"2019","unstructured":"McIntosh A, Mela V, Harty C, Minogue AM, Costello DA, Kerskens C, et al. Iron accumulation in microglia triggers a cascade of events that leads to altered metabolism and compromised function in APP\/PS1 mice. Brain Pathol 2019, 29: 606\u2013621.","journal-title":"Brain Pathol"},{"key":"1693_CR30","doi-asserted-by":"publisher","first-page":"102846","DOI":"10.1016\/j.redox.2023.102846","volume":"66","author":"M Sangineto","year":"2023","unstructured":"Sangineto M, Ciarnelli M, Cassano T, Radesco A, Moola A, Bukke VN, et al. Metabolic reprogramming in inflammatory microglia indicates a potential way of targeting inflammation in Alzheimer\u2019s disease. Redox Biol 2023, 66: 102846.","journal-title":"Redox Biol"},{"key":"1693_CR31","doi-asserted-by":"publisher","first-page":"3458","DOI":"10.1016\/j.neuron.2022.10.020","volume":"110","author":"RC Paolicelli","year":"2022","unstructured":"Paolicelli RC, Sierra A, Stevens B, Tremblay ME, Aguzzi A, Ajami B, et al. Microglia states and nomenclature: A field at its crossroads. Neuron 2022, 110: 3458\u20133483.","journal-title":"Neuron"},{"key":"1693_CR32","doi-asserted-by":"publisher","first-page":"10129","DOI":"10.1523\/JNEUROSCI.1202-06.2006","volume":"26","author":"H Oakley","year":"2006","unstructured":"Oakley H, Cole SL, Logan S, Maus E, Shao P, Craft J, et al. Intraneuronal \u03b2-amyloid aggregates, neurodegeneration, and neuron loss in transgenic mice with five familial Alzheimer\u2019s disease mutations: Potential factors in amyloid plaque formation. J Neurosci 2006, 26: 10129\u201310140.","journal-title":"J Neurosci"},{"key":"1693_CR33","doi-asserted-by":"publisher","first-page":"2293","DOI":"10.3390\/ijms20092293","volume":"20","author":"CRA Batista","year":"2019","unstructured":"Batista CRA, Gomes GF, Candelario-Jalil E, Fiebich BL, de Oliveira ACP. Lipopolysaccharide-induced neuroinflammation as a bridge to understand neurodegeneration. Int J Mol Sci 2019, 20: 2293.","journal-title":"Int J Mol Sci"},{"key":"1693_CR34","doi-asserted-by":"publisher","first-page":"453","DOI":"10.1002\/glia.20467","volume":"55","author":"L Qin","year":"2007","unstructured":"Qin L, Wu X, Block ML, Liu Y, Breese GR, Hong JS, et al. Systemic LPS causes chronic neuroinflammation and progressive neurodegeneration. Glia 2007, 55: 453\u2013462.","journal-title":"Glia"},{"key":"1693_CR35","doi-asserted-by":"publisher","first-page":"366","DOI":"10.1186\/s12974-020-02019-5","volume":"17","author":"P Honarpisheh","year":"2020","unstructured":"Honarpisheh P, Lee J, Banerjee A, Blasco-Conesa MP, Honarpisheh P, D\u2019Aigle J, et al. Potential caveats of putative microglia-specific markers for assessment of age-related cerebrovascular neuroinflammation. J Neuroinflammation 2020, 17: 366.","journal-title":"J Neuroinflammation"},{"key":"1693_CR36","doi-asserted-by":"publisher","first-page":"1031","DOI":"10.1002\/glia.23760","volume":"68","author":"Y Hu","year":"2020","unstructured":"Hu Y, Mai W, Chen L, Cao K, Zhang B, Zhang Z, et al. mTOR-mediated metabolic reprogramming shapes distinct microglia functions in response to lipopolysaccharide and ATP. Glia 2020, 68: 1031\u20131045.","journal-title":"Glia"},{"key":"1693_CR37","doi-asserted-by":"publisher","first-page":"1047","DOI":"10.1002\/glia.23587","volume":"67","author":"S Nair","year":"2019","unstructured":"Nair S, Sobotka KS, Joshi P, Gressens P, Fleiss B, Thornton C, et al. Lipopolysaccharide-induced alteration of mitochondrial morphology induces a metabolic shift in microglia modulating the inflammatory response in vitro and in vivo. Glia 2019, 67: 1047\u20131061.","journal-title":"Glia"},{"key":"1693_CR38","doi-asserted-by":"publisher","first-page":"56","DOI":"10.1186\/s13195-015-0139-9","volume":"7","author":"DG Walker","year":"2015","unstructured":"Walker DG, Lue LF. Immune phenotypes of microglia in human neurodegenerative disease: Challenges to detecting microglial polarization in human brains. Alzheimers Res Ther 2015, 7: 56.","journal-title":"Alzheimers Res Ther"},{"key":"1693_CR39","doi-asserted-by":"publisher","first-page":"1830","DOI":"10.1016\/j.immuni.2025.04.018","volume":"58","author":"J Liu","year":"2025","unstructured":"Liu J, Wang Z, Liang W, Zhang Z, Deng Y, Chen X et al (2025) Microglial TMEM119 binds to amyloid-\u03b2 to promote its clearance in an A\u03b2-depositing mouse model of Alzheimer\u2019s disease. Immunity 58:1830\u20131846.e7","journal-title":"Immunity"},{"key":"1693_CR40","doi-asserted-by":"publisher","first-page":"6","DOI":"10.1186\/s12868-024-00846-3","volume":"25","author":"W Ma","year":"2024","unstructured":"Ma W, Oswald J, Rios Angulo A, Chen Q. Tmem119 expression is downregulated in a subset of brain metastasis-associated microglia. BMC Neurosci 2024, 25: 6.","journal-title":"BMC Neurosci"},{"key":"1693_CR41","doi-asserted-by":"publisher","first-page":"375","DOI":"10.1016\/j.ajpath.2015.10.010","volume":"186","author":"A Serrano-Pozo","year":"2016","unstructured":"Serrano-Pozo A, Betensky RA, Frosch MP, Hyman BT. Plaque-associated local toxicity increases over the clinical course of Alzheimer disease. Am J Pathol 2016, 186: 375\u2013384.","journal-title":"Am J Pathol"},{"key":"1693_CR42","doi-asserted-by":"publisher","first-page":"443","DOI":"10.1016\/j.cmet.2018.12.004","volume":"29","author":"S Zhang","year":"2019","unstructured":"Zhang S, Weinberg S, DeBerge M, Gainullina A, Schipma M, Kinchen JM et al (2019) Efferocytosis fuels requirements of fatty acid oxidation and the electron transport chain to polarize macrophages for tissue repair. Cell Metab 29:443\u2013456.e5","journal-title":"Cell Metab"},{"key":"1693_CR43","doi-asserted-by":"publisher","first-page":"254","DOI":"10.1038\/s41577-019-0240-6","volume":"20","author":"AC Doran","year":"2020","unstructured":"Doran AC, Yurdagul A, Tabas I. Efferocytosis in health and disease. Nat Rev Immunol 2020, 20: 254\u2013267.","journal-title":"Nat Rev Immunol"},{"key":"1693_CR44","doi-asserted-by":"publisher","first-page":"245","DOI":"10.1016\/j.immuni.2009.06.018","volume":"31","author":"N A-Gonzalez","year":"2009","unstructured":"A-Gonzalez N, Bensinger SJ, Hong C, Beceiro S, Bradley MN, Zelcer N, et al. Apoptotic cells promote their own clearance and immune tolerance through activation of the nuclear receptor LXR. Immunity 2009, 31: 245\u2013258.","journal-title":"Immunity"},{"key":"1693_CR45","doi-asserted-by":"publisher","first-page":"1736","DOI":"10.1038\/s42255-024-01115-7","volume":"6","author":"SR Sukka","year":"2024","unstructured":"Sukka SR, Ampomah PB, Darville LNF, Ngai D, Wang X, Kuriakose G, et al. Efferocytosis drives a tryptophan metabolism pathway in macrophages to promote tissue resolution. Nat Metab 2024, 6: 1736\u20131755.","journal-title":"Nat Metab"},{"key":"1693_CR46","doi-asserted-by":"publisher","first-page":"1182","DOI":"10.1126\/science.abl4430","volume":"375","author":"MH Raymond","year":"2022","unstructured":"Raymond MH, Davidson AJ, Shen Y, Tudor DR, Lucas CD, Morioka S, et al. Live cell tracking of macrophage efferocytosis during Drosophilaembryo development in vivo. Science 2022, 375: 1182\u20131187.","journal-title":"Science"},{"key":"1693_CR47","doi-asserted-by":"publisher","first-page":"3513","DOI":"10.1016\/j.neuron.2022.10.015","volume":"110","author":"C Romero-Molina","year":"2022","unstructured":"Romero-Molina C, Garretti F, Andrews SJ, Marcora E, Goate AM. Microglial efferocytosis: Diving into the Alzheimer\u2019s disease gene pool. Neuron 2022, 110: 3513\u20133533.","journal-title":"Neuron"},{"key":"1693_CR48","doi-asserted-by":"publisher","first-page":"27876","DOI":"10.1074\/jbc.M112.377549","volume":"287","author":"JG Cash","year":"2012","unstructured":"Cash JG, Kuhel DG, Basford JE, Jaeschke A, Chatterjee TK, Weintraub NL, et al. Apolipoprotein E4 impairs macrophage efferocytosis and potentiates apoptosis by accelerating endoplasmic reticulum stress. J Biol Chem 2012, 287: 27876\u201327884.","journal-title":"J Biol Chem"},{"key":"1693_CR49","doi-asserted-by":"publisher","first-page":"430","DOI":"10.1016\/j.tem.2023.05.002","volume":"34","author":"LG Yang","year":"2023","unstructured":"Yang LG, March ZM, Stephenson RA, Narayan PS. Apolipoprotein E in lipid metabolism and neurodegenerative disease. Trends Endocrinol Metab 2023, 34: 430\u2013445.","journal-title":"Trends Endocrinol Metab"},{"key":"1693_CR50","doi-asserted-by":"publisher","first-page":"5","DOI":"10.6026\/97320630002005","volume":"2","author":"L Kumar","year":"2007","unstructured":"Kumar L, Futschik ME. Mfuzz: A software package for soft clustering of microarray data. Bioinformation 2007, 2: 5\u20137.","journal-title":"Bioinformation"},{"key":"1693_CR51","doi-asserted-by":"publisher","first-page":"75","DOI":"10.1186\/s13024-022-00577-1","volume":"17","author":"N Wang","year":"2022","unstructured":"Wang N, Wang M, Jeevaratnam S, Rosenberg C, Ikezu TC, Shue F, et al. Opposing effects of apoE2 and apoE4 on microglial activation and lipid metabolism in response to demyelination. Mol Neurodegener 2022, 17: 75.","journal-title":"Mol Neurodegener"},{"key":"1693_CR52","doi-asserted-by":"publisher","first-page":"99","DOI":"10.1186\/s13024-023-00693-6","volume":"18","author":"G Eskandari-Sedighi","year":"2023","unstructured":"Eskandari-Sedighi G, Blurton-Jones M. Microglial APOE4: More is less and less is more. Mol Neurodegener 2023, 18: 99.","journal-title":"Mol Neurodegener"},{"key":"1693_CR53","doi-asserted-by":"publisher","first-page":"6292","DOI":"10.1073\/pnas.1705080114","volume":"114","author":"C Frieden","year":"2017","unstructured":"Frieden C, Wang H, Ho CMW. A mechanism for lipid binding to apoE and the role of intrinsically disordered regions coupled to domain\u2013domain interactions. Proc Natl Acad Sci USA 2017, 114: 6292\u20136297.","journal-title":"Proc Natl Acad Sci USA"},{"key":"1693_CR54","doi-asserted-by":"publisher","first-page":"2213","DOI":"10.1016\/j.cell.2022.05.017","volume":"185","author":"J Tcw","year":"2022","unstructured":"Tcw J, Qian L, Pipalia NH, Chao MJ, Liang SA, Shi Y et al (2022) Cholesterol and matrisome pathways dysregulated in astrocytes and microglia. Cell 185:2213\u20132233.e25","journal-title":"Cell"},{"key":"1693_CR55","doi-asserted-by":"publisher","first-page":"194","DOI":"10.1038\/s41593-019-0566-1","volume":"23","author":"J Marschallinger","year":"2020","unstructured":"Marschallinger J, Iram T, Zardeneta M, Lee SE, Lehallier B, Haney MS, et al. Lipid-droplet-accumulating microglia represent a dysfunctional and proinflammatory state in the aging brain. Nat Neurosci 2020, 23: 194\u2013208.","journal-title":"Nat Neurosci"},{"key":"1693_CR56","doi-asserted-by":"publisher","first-page":"1536","DOI":"10.1016\/j.immuni.2025.04.029","volume":"58","author":"P Prakash","year":"2025","unstructured":"Prakash P, Manchanda P, Paouri E, Bisht K, Sharma K, Rajpoot J, et al. Amyloid-\u03b2 induces lipid droplet-mediated microglial dysfunction via the enzyme DGAT2 in Alzheimer\u2019s disease. Immunity 2025, 58: 1536\u20131552.e8.","journal-title":"Immunity"},{"key":"1693_CR57","doi-asserted-by":"publisher","first-page":"385","DOI":"10.1038\/s43587-021-00054-2","volume":"1","author":"R March-Diaz","year":"2021","unstructured":"March-Diaz R, Lara-Ure\u00f1a N, Romero-Molina C, Heras-Garvin A, Ortega-de San Luis C, Alvarez-Vergara MI, et al. Hypoxia compromises the mitochondrial metabolism of Alzheimer\u2019s disease microglia via HIF1. Nat Aging 2021, 1: 385\u2013399.","journal-title":"Nat Aging"},{"key":"1693_CR58","doi-asserted-by":"publisher","first-page":"37","DOI":"10.1186\/s13024-025-00825-0","volume":"20","author":"ES Jung","year":"2025","unstructured":"Jung ES, Choi H, Mook-Jung I. Decoding microglial immunometabolism: A new frontier in Alzheimer\u2019s disease research. Mol Neurodegener 2025, 20: 37.","journal-title":"Mol Neurodegener"},{"key":"1693_CR59","doi-asserted-by":"publisher","first-page":"304","DOI":"10.1186\/s12974-016-0772-7","volume":"13","author":"L Yang","year":"2016","unstructured":"Yang L, Liu CC, Zheng H, Kanekiyo T, Atagi Y, Jia L, et al. LRP1 modulates the microglial immune response via regulation of JNK and NF-\u03baB signaling pathways. J Neuroinflammation 2016, 13: 304.","journal-title":"J Neuroinflammation"},{"key":"1693_CR60","doi-asserted-by":"publisher","first-page":"444","DOI":"10.1002\/glia.20772","volume":"57","author":"A Pocivavsek","year":"2009","unstructured":"Pocivavsek A, Burns MP, Rebeck GW. Low-density lipoprotein receptors regulate microglial inflammation through c-Jun N-terminal kinase. Glia 2009, 57: 444\u2013453.","journal-title":"Glia"},{"key":"1693_CR61","doi-asserted-by":"publisher","first-page":"723","DOI":"10.1016\/j.immuni.2023.03.007","volume":"56","author":"AM Kabat","year":"2023","unstructured":"Kabat AM, Pearce EL, Pearce EJ. Metabolism in type 2 immune responses. Immunity 2023, 56: 723\u2013741.","journal-title":"Immunity"},{"issue":"5123","key":"1693_CR62","doi-asserted-by":"publisher","first-page":"921","DOI":"10.1126\/science.8346443","volume":"261","author":"EH Corder","year":"1993","unstructured":"Corder EH, Saunders AM, Strittmatter WJ, Schmechel DE, Gaskell PC, Small GW, et al. Gene dose of apolipoprotein E type 4 allele and the risk of Alzheimer\u2019s disease in late onset families. Science 1993, 261(5123): 921\u2013923.","journal-title":"Science"}],"container-title":["Neuroscience Bulletin"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1007\/s12264-026-01693-4.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/article\/10.1007\/s12264-026-01693-4","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1007\/s12264-026-01693-4.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,8,8]],"date-time":"2026-08-08T17:02:23Z","timestamp":1786208543000},"score":1,"resource":{"primary":{"URL":"https:\/\/link.springer.com\/10.1007\/s12264-026-01693-4"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,8,8]]},"references-count":62,"alternative-id":["1693"],"URL":"https:\/\/doi.org\/10.1007\/s12264-026-01693-4","relation":{},"ISSN":["1673-7067","1995-8218"],"issn-type":[{"value":"1673-7067","type":"print"},{"value":"1995-8218","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,8,8]]},"assertion":[{"value":"15 March 2026","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"30 July 2026","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"8 August 2026","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"Chunjiu Zhong holds shares in Shanghai Raising Pharmaceutical Co., Ltd., which is dedicated to the development of drugs for the prevention and treatment of AD. The other authors declare no competing interests.","order":1,"name":"Ethics","label":"Conflict of interest","group":{"name":"EthicsHeading","label":"Ethics"}}]}}