{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,13]],"date-time":"2026-10-13T21:10:37Z","timestamp":1791925837866,"version":"4.3.4"},"reference-count":76,"publisher":"Springer Science and Business Media LLC","issue":"2","license":[{"start":{"date-parts":[[2025,1,1]],"date-time":"2025-01-01T00:00:00Z","timestamp":1735689600000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.springernature.com\/gp\/researchers\/text-and-data-mining"},{"start":{"date-parts":[[2025,1,1]],"date-time":"2025-01-01T00:00:00Z","timestamp":1735689600000},"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":["Cell Mol Immunol"],"DOI":"10.1038\/s41423-024-01235-w","type":"journal-article","created":{"date-parts":[[2025,1,1]],"date-time":"2025-01-01T01:02:15Z","timestamp":1735693335000},"page":"134-149","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":18,"title":["Demyelination-derived lysophosphatidylserine promotes microglial dysfunction and neuropathology in a mouse model of Alzheimer\u2019s disease"],"prefix":"10.1038","volume":"22","author":[{"ORCID":"https:\/\/orcid.org\/0009-0008-7770-6198","authenticated-orcid":false,"given":"Yubo","family":"Zhou","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zonghui","family":"Huang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6705-4033","authenticated-orcid":false,"given":"Bolong","family":"Lin","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ming","family":"Ma","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yize","family":"Hao","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Juanjuan","family":"Liu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wen","family":"Xu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Guangming","family":"Huang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wei","family":"Mo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaqiong","family":"Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8327-3079","authenticated-orcid":false,"given":"Wei","family":"Jiang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3351-6420","authenticated-orcid":false,"given":"Rongbin","family":"Zhou","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2025,1,1]]},"reference":[{"key":"1235_CR1","doi-asserted-by":"publisher","first-page":"353","DOI":"10.1126\/science.1072994","volume":"297","author":"J Hardy","year":"2002","unstructured":"Hardy J, Selkoe DJ. The amyloid hypothesis of Alzheimer\u2019s disease: progress and problems on the road to therapeutics. Science. 2002;297:353\u20136.","journal-title":"Science"},{"key":"1235_CR2","doi-asserted-by":"publisher","first-page":"184","DOI":"10.1126\/science.1566067","volume":"256","author":"JA Hardy","year":"1992","unstructured":"Hardy JA, Higgins GA. Alzheimer\u2019s disease: the amyloid cascade hypothesis. Science. 1992;256:184\u20135.","journal-title":"Science"},{"key":"1235_CR3","doi-asserted-by":"publisher","first-page":"306","DOI":"10.1038\/s41573-022-00391-w","volume":"21","author":"E Karran","year":"2022","unstructured":"Karran E, De Strooper B. The amyloid hypothesis in Alzheimer disease: new insights from new therapeutics. Nat Rev Drug Discov. 2022;21:306\u201318.","journal-title":"Nat Rev Drug Discov"},{"key":"1235_CR4","doi-asserted-by":"publisher","first-page":"534","DOI":"10.1016\/j.neuron.2008.11.007","volume":"60","author":"SA Small","year":"2008","unstructured":"Small SA, Duff K. Linking Abeta and tau in late-onset Alzheimer\u2019s disease: a dual pathway hypothesis. Neuron. 2008;60:534\u201342.","journal-title":"Neuron"},{"key":"1235_CR5","doi-asserted-by":"publisher","first-page":"794","DOI":"10.1038\/nn.4017","volume":"18","author":"K Herrup","year":"2015","unstructured":"Herrup K. The case for rejecting the amyloid cascade hypothesis. Nat Neurosci. 2015;18:794\u20139.","journal-title":"Nat Neurosci"},{"key":"1235_CR6","doi-asserted-by":"publisher","first-page":"232","DOI":"10.1038\/d41586-023-01537-5","volume":"617","author":"S Reardon","year":"2023","unstructured":"Reardon S. Alzheimer\u2019s drug donanemab: what promising trial means for treatments. Nature. 2023;617:232\u20133.","journal-title":"Nature"},{"key":"1235_CR7","doi-asserted-by":"publisher","first-page":"571","DOI":"10.1126\/science.adi6515","volume":"380","author":"J Travis","year":"2023","unstructured":"Travis J. Latest Alzheimer\u2019s antibody is \u2018not a miracle drug\u2019. Science. 2023;380:571.","journal-title":"Science"},{"key":"1235_CR8","doi-asserted-by":"publisher","first-page":"157","DOI":"10.1038\/s41582-020-00435-y","volume":"17","author":"F Leng","year":"2021","unstructured":"Leng F, Edison P. Neuroinflammation and microglial activation in Alzheimer disease: where do we go from here? Nat Rev Neurol. 2021;17:157\u201372.","journal-title":"Nat Rev Neurol"},{"key":"1235_CR9","doi-asserted-by":"publisher","first-page":"674","DOI":"10.1038\/nature11729","volume":"493","author":"MT Heneka","year":"2013","unstructured":"Heneka MT, Kummer MP, Stutz A, Delekate A, Schwartz S, Vieira-Saecker A, et al. NLRP3 is activated in Alzheimer\u2019s disease and contributes to pathology in APP\/PS1 mice. Nature. 2013;493:674\u20138.","journal-title":"Nature"},{"key":"1235_CR10","doi-asserted-by":"publisher","first-page":"1200","DOI":"10.1136\/jnnp.74.9.1200","volume":"74","author":"E Tarkowski","year":"2003","unstructured":"Tarkowski E, Andreasen N, Tarkowski A, Blennow K. Intrathecal inflammation precedes development of Alzheimer\u2019s disease. J Neurol Neurosurg Psychiatry. 2003;74:1200\u20135.","journal-title":"J Neurol Neurosurg Psychiatry"},{"key":"1235_CR11","doi-asserted-by":"publisher","first-page":"e59586","DOI":"10.1371\/journal.pone.0059586","volume":"8","author":"AL Wright","year":"2013","unstructured":"Wright AL, Zinn R, Hohensinn B, Konen LM, Beynon SB, Tan RP, et al. Neuroinflammation and neuronal loss precede Abeta plaque deposition in the hAPP-J20 mouse model of Alzheimer\u2019s disease. PLoS One. 2013;8:e59586.","journal-title":"PLoS One"},{"key":"1235_CR12","doi-asserted-by":"publisher","first-page":"337","DOI":"10.1016\/j.neuron.2007.01.010","volume":"53","author":"Y Yoshiyama","year":"2007","unstructured":"Yoshiyama Y, Higuchi M, Zhang B, Huang SM, Iwata N, Saido TC, et al. Synapse loss and microglial activation precede tangles in a P301S tauopathy mouse model. Neuron. 2007;53:337\u201351.","journal-title":"Neuron"},{"key":"1235_CR13","doi-asserted-by":"publisher","first-page":"56","DOI":"10.1212\/01.wnl.0000338622.27876.0d","volume":"72","author":"A Okello","year":"2009","unstructured":"Okello A, Edison P, Archer HA, Turkheimer FE, Kennedy J, Bullock R, et al. Microglial activation and amyloid deposition in mild cognitive impairment: a PET study. Neurology. 2009;72:56\u201362.","journal-title":"Neurology"},{"key":"1235_CR14","doi-asserted-by":"publisher","first-page":"e1331","DOI":"10.1212\/WNL.0000000000007133","volume":"92","author":"GD Femminella","year":"2019","unstructured":"Femminella GD, Dani M, Wood M, Fan Z, Calsolaro V, Atkinson R, et al. Microglial activation in early Alzheimer trajectory is associated with higher gray matter volume. Neurology. 2019;92:e1331\u2013e1343.","journal-title":"Neurology"},{"key":"1235_CR15","doi-asserted-by":"publisher","first-page":"2228","DOI":"10.1093\/brain\/awt145","volume":"136","author":"WC Kreisl","year":"2013","unstructured":"Kreisl WC, Lyoo CH, McGwier M, Snow J, Jenko KJ, Kimura N, et al. In vivo radioligand binding to translocator protein correlates with severity of Alzheimer\u2019s disease. Brain. 2013;136:2228\u201338.","journal-title":"Brain"},{"key":"1235_CR16","doi-asserted-by":"publisher","first-page":"111","DOI":"10.1007\/s004060050027","volume":"248","author":"HJ M\u00f6ller","year":"1998","unstructured":"M\u00f6ller HJ, Graeber MB. The case described by Alois Alzheimer in 1911. Historical and conceptual perspectives based on the clinical record and neurohistological sections. Eur Arch Psychiatry Clin Neurosci. 1998;248:111\u201322.","journal-title":"Eur Arch Psychiatry Clin Neurosci"},{"key":"1235_CR17","doi-asserted-by":"publisher","first-page":"89","DOI":"10.1016\/j.neurobiolaging.2016.03.027","volume":"43","author":"TA Couttas","year":"2016","unstructured":"Couttas TA, Kain N, Suchowerska AK, Quek LE, Turner N, Fath T, et al. Loss of ceramide synthase 2 activity, necessary for myelin biosynthesis, precedes tau pathology in the cortical pathogenesis of Alzheimer\u2019s disease. Neurobiol Aging. 2016;43:89\u2013100.","journal-title":"Neurobiol Aging"},{"key":"1235_CR18","doi-asserted-by":"publisher","first-page":"54","DOI":"10.1002\/glia.20734","volume":"57","author":"MK Desai","year":"2009","unstructured":"Desai MK, Sudol KL, Janelsins MC, Mastrangelo MA, Frazer ME, Bowers WJ. Triple-transgenic Alzheimer\u2019s disease mice exhibit region-specific abnormalities in brain myelination patterns prior to appearance of amyloid and tau pathology. Glia. 2009;57:54\u201365.","journal-title":"Glia"},{"key":"1235_CR19","doi-asserted-by":"publisher","first-page":"1282","DOI":"10.1126\/science.1105681","volume":"307","author":"GB Stokin","year":"2005","unstructured":"Stokin GB, Lillo C, Falzone TL, Brusch RG, Rockenstein E, Mount SL, et al. Axonopathy and transport deficits early in the pathogenesis of Alzheimer\u2019s disease. Science. 2005;307:1282\u20138.","journal-title":"Science"},{"key":"1235_CR20","doi-asserted-by":"publisher","first-page":"eabb8680","DOI":"10.1126\/sciadv.abb8680","volume":"6","author":"X Zhang","year":"2020","unstructured":"Zhang X, Wang R, Hu D, Sun X, Fujioka H, Lundberg K, et al. Oligodendroglial glycolytic stress triggers inflammasome activation and neuropathology in Alzheimer\u2019s disease. Sci Adv. 2020;6:eabb8680.","journal-title":"Sci Adv"},{"key":"1235_CR21","doi-asserted-by":"crossref","unstructured":"Depp, C, et al. Myelin dysfunction drives amyloid-beta deposition in models of Alzheimer\u2019s disease. Nature. 2023;618:349\u2013357.","DOI":"10.1038\/s41586-023-06120-6"},{"key":"1235_CR22","doi-asserted-by":"publisher","first-page":"107","DOI":"10.1056\/NEJMoa1211103","volume":"368","author":"T Jonsson","year":"2013","unstructured":"Jonsson T, Stefansson H, Steinberg S, Jonsdottir I, Jonsson PV, Snaedal J, et al. Variant of TREM2 associated with the risk of Alzheimer\u2019s disease. N. Engl J Med. 2013;368:107\u201316.","journal-title":"N. Engl J Med"},{"key":"1235_CR23","doi-asserted-by":"publisher","first-page":"759","DOI":"10.1016\/j.neuron.2020.02.008","volume":"105","author":"EC Damisah","year":"2020","unstructured":"Damisah EC, Rai A, Grutzendler J. TREM2: modulator of lipid metabolism in microglia. Neuron. 2020;105:759\u201361.","journal-title":"Neuron"},{"key":"1235_CR24","doi-asserted-by":"publisher","first-page":"522","DOI":"10.1038\/s41582-020-0404-9","volume":"16","author":"H Wood","year":"2020","unstructured":"Wood H. TREM2 activation promotes remyelination. Nat Rev Neurol. 2020;16:522\u2013522.","journal-title":"Nat Rev Neurol"},{"key":"1235_CR25","doi-asserted-by":"publisher","DOI":"10.1186\/s13024-022-00542-y","volume":"17","author":"R-Y Li","year":"2022","unstructured":"Li R-Y, Qin Q, Yang HC, Wang YY, Mi YX, Yin YS, et al. TREM2 in the pathogenesis of AD: a lipid metabolism regulator and potential metabolic therapeutic target. Mol Neurodegeneration. 2022;17:40.","journal-title":"Mol Neurodegeneration"},{"key":"1235_CR26","doi-asserted-by":"publisher","first-page":"433","DOI":"10.1002\/jnr.490380409","volume":"38","author":"K Williams","year":"1994","unstructured":"Williams K, Ulvestad E, Waage A, Antel JP, McLaurin J. Activation of adult human derived microglia by myelin phagocytosis in vitro. J Neurosci Res. 1994;38:433\u201343.","journal-title":"J Neurosci Res"},{"key":"1235_CR27","doi-asserted-by":"publisher","first-page":"684","DOI":"10.1126\/science.aan4183","volume":"359","author":"L Cantuti-Castelvetri","year":"2018","unstructured":"Cantuti-Castelvetri L, Fitzner D, Bosch-Queralt M, Weil MT, Su M, Sen P, et al. Defective cholesterol clearance limits remyelination in the aged central nervous system. Science. 2018;359:684\u20138.","journal-title":"Science"},{"key":"1235_CR28","doi-asserted-by":"publisher","first-page":"1131","DOI":"10.1038\/s41423-024-01204-3","volume":"21","author":"B Lin","year":"2024","unstructured":"Lin B, Zhou Y, Huang Z, Ma M, Qi M, Jiang Z, et al. GPR34 senses demyelination to promote neuroinflammation and pathologies. Cell Mol Immunol. 2024;21:1131\u20131144.","journal-title":"Cell Mol Immunol"},{"key":"1235_CR29","doi-asserted-by":"publisher","first-page":"183","DOI":"10.1006\/jmbi.1998.1677","volume":"278","author":"J McLaurin","year":"1998","unstructured":"McLaurin J, Franklin T, Chakrabartty A, Fraser PE. Phosphatidylinositol and inositol involvement in Alzheimer amyloid-\u03b2 fibril growth and arrest. J Mol Biol. 1998;278:183\u201394.","journal-title":"J Mol Biol"},{"key":"1235_CR30","doi-asserted-by":"publisher","first-page":"614855","DOI":"10.3389\/fnins.2021.614855","volume":"15","author":"K Ando","year":"2021","unstructured":"Ando K, Erneux C, Homa M, Houben S, de Fisenne MA, Brion JP, et al. Dysregulation of phosphoinositide 5-phosphatases and phosphoinositides in Alzheimer\u2019s disease. Front Neurosci. 2021;15:614855.","journal-title":"Front Neurosci"},{"key":"1235_CR31","doi-asserted-by":"publisher","first-page":"975176","DOI":"10.3389\/fnagi.2022.975176","volume":"14","author":"X Ma","year":"2022","unstructured":"Ma X, Li X, Wang W, Zhang M, Yang B, Miao Z. Phosphatidylserine, inflammation, and central nervous system diseases. Front Aging Neurosci. 2022;14:975176.","journal-title":"Front Aging Neurosci"},{"key":"1235_CR32","doi-asserted-by":"publisher","first-page":"164","DOI":"10.1038\/nchembio.1721","volume":"11","author":"SS Kamat","year":"2015","unstructured":"Kamat SS, Camara K, Parsons WH, Chen DH, Dix MM, Bird TD, et al. Immunomodulatory lysophosphatidylserines are regulated by ABHD16A and ABHD12 interplay. Nat Chem Biol. 2015;11:164\u201371.","journal-title":"Nat Chem Biol"},{"key":"1235_CR33","doi-asserted-by":"publisher","first-page":"26","DOI":"10.1016\/S1388-1981(02)00134-8","volume":"1582","author":"J Aoki","year":"2002","unstructured":"Aoki J, Nagai Y, Hosono H, Inoue K, Arai H. Structure and function of phosphatidylserine-specific phospholipase A1. Biochim Biophys Acta. 2002;1582:26\u201332.","journal-title":"Biochim Biophys Acta"},{"key":"1235_CR34","doi-asserted-by":"publisher","first-page":"381","DOI":"10.1007\/s00232-020-00133-2","volume":"253","author":"K Shanbhag","year":"2020","unstructured":"Shanbhag K, Mhetre A, Khandelwal N, Kamat SS. The lysophosphatidylserines\u2014an emerging class of signaling lysophospholipids. J Membr Biol. 2020;253:381\u201397.","journal-title":"J Membr Biol"},{"key":"1235_CR35","doi-asserted-by":"publisher","first-page":"536","DOI":"10.1016\/j.cell.2019.05.056","volume":"178","author":"BL Heckmann","year":"2019","unstructured":"Heckmann BL, Teubner BJW, Tummers B, Boada-Romero E, Harris L, Yang M, et al. LC3-associated endocytosis facilitates \u03b2-amyloid clearance and mitigates neurodegeneration in murine Alzheimer\u2019s disease. Cell. 2019;178:536\u2013551.e14.","journal-title":"Cell"},{"key":"1235_CR36","doi-asserted-by":"publisher","first-page":"4135","DOI":"10.1016\/j.cell.2022.09.030","volume":"185","author":"H Ennerfelt","year":"2022","unstructured":"Ennerfelt H, Frost EL, Shapiro DA, Holliday C, Zengeler KE, Voithofer G, et al. SYK coordinates neuroprotective microglial responses in neurodegenerative disease. Cell. 2022;185:4135\u20134152.","journal-title":"Cell"},{"key":"1235_CR37","doi-asserted-by":"publisher","first-page":"329","DOI":"10.1007\/s00401-013-1152-3","volume":"126","author":"PC Kandalepas","year":"2013","unstructured":"Kandalepas PC, Sadleir KR, Eimer WA, Zhao J, Nicholson DA, Vassar R. The Alzheimer\u2019s beta-secretase BACE1 localizes to normal presynaptic terminals and to dystrophic presynaptic terminals surrounding amyloid plaques. Acta Neuropathol. 2013;126:329\u201352.","journal-title":"Acta Neuropathol"},{"key":"1235_CR38","doi-asserted-by":"publisher","first-page":"879","DOI":"10.1016\/j.immuni.2022.03.018","volume":"55","author":"ER Roy","year":"2022","unstructured":"Roy ER, Chiu G, Li S, Propson NE, Kanchi R, Wang B, et al. Concerted type I interferon signaling in microglia and neural cells promotes memory impairment associated with amyloid \u03b2 plaques. Immunity. 2022;55:879\u2013894.e6.","journal-title":"Immunity"},{"key":"1235_CR39","doi-asserted-by":"publisher","first-page":"1468","DOI":"10.1002\/glia.22367","volume":"60","author":"T Clarner","year":"2012","unstructured":"Clarner T, Diederichs F, Berger K, Denecke B, Gan L, van der Valk P, et al. Myelin debris regulates inflammatory responses in an experimental demyelination animal model and multiple sclerosis lesions. Glia. 2012;60:1468\u201380.","journal-title":"Glia"},{"key":"1235_CR40","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1186\/s12974-015-0332-6","volume":"12","author":"IC Hoogland","year":"2015","unstructured":"Hoogland IC, Houbolt C, van Westerloo DJ, van Gool WA, van de Beek D. Systemic inflammation and microglial activation: systematic review of animal experiments. J neuroinflammation. 2015;12:1\u201313.","journal-title":"J neuroinflammation"},{"key":"1235_CR41","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\u2013581.e9.","journal-title":"Immunity"},{"key":"1235_CR42","doi-asserted-by":"publisher","first-page":"166814","DOI":"10.1016\/j.bbadis.2023.166814","volume":"1869","author":"XY Chen","year":"2023","unstructured":"Chen XY, Feng SN, Bao Y, Zhou YX, Ba F. Identification of Clec7a as the therapeutic target of rTMS in alleviating Parkinson\u2019s disease: targeting neuroinflammation. Biochim Biophys Acta Mol Basis Dis. 2023;1869:166814.","journal-title":"Biochim Biophys Acta Mol Basis Dis"},{"key":"1235_CR43","doi-asserted-by":"publisher","first-page":"497","DOI":"10.1007\/s12013-021-00988-9","volume":"79","author":"J Omi","year":"2021","unstructured":"Omi J, Kano K, Aoki J. Current knowledge on the biology of lysophosphatidylserine as an emerging bioactive lipid. Cell Biochem Biophys. 2021;79:497\u2013508.","journal-title":"Cell Biochem Biophys"},{"key":"1235_CR44","doi-asserted-by":"publisher","first-page":"1021","DOI":"10.1038\/nmeth.2172","volume":"9","author":"A Inoue","year":"2012","unstructured":"Inoue A, Ishiguro J, Kitamura H, Arima N, Okutani M, Shuto A, et al. TGF\u03b1 shedding assay: an accurate and versatile method for detecting GPCR activation. Nat methods. 2012;9:1021\u20139.","journal-title":"Nat methods"},{"key":"1235_CR45","doi-asserted-by":"publisher","first-page":"317","DOI":"10.1038\/s41586-023-06812-z","volume":"624","author":"Z Yao","year":"2023","unstructured":"Yao Z, van Velthoven C, Kunst M, Zhang M, McMillen D, Lee C, et al. A high-resolution transcriptomic and spatial atlas of cell types in the whole mouse brain. Nature. 2023;624:317\u201332.","journal-title":"Nature"},{"key":"1235_CR46","doi-asserted-by":"publisher","first-page":"1896","DOI":"10.1038\/nn.3554","volume":"16","author":"SE Hickman","year":"2013","unstructured":"Hickman SE, Kingery ND, Ohsumi TK, Borowsky ML, Wang LC, Means TK, et al. The microglial sensome revealed by direct RNA sequencing. Nat Neurosci. 2013;16:1896\u2013905.","journal-title":"Nat Neurosci"},{"key":"1235_CR47","doi-asserted-by":"publisher","first-page":"131","DOI":"10.1038\/nn.3599","volume":"17","author":"O Butovsky","year":"2014","unstructured":"Butovsky O, Jedrychowski MP, Moore CS, Cialic R, Lanser AJ, Gabriely G, et al. Identification of a unique TGF-beta-dependent molecular and functional signature in microglia. Nat Neurosci. 2014;17:131\u201343.","journal-title":"Nat Neurosci"},{"key":"1235_CR48","doi-asserted-by":"publisher","first-page":"71","DOI":"10.1007\/s10571-014-0101-6","volume":"35","author":"Y Yu","year":"2015","unstructured":"Yu Y, Ye RD. Microglial A\u03b2 receptors in Alzheimer\u2019s disease. Cell Mol Neurobiol. 2015;35:71\u201383.","journal-title":"Cell Mol Neurobiol"},{"key":"1235_CR49","doi-asserted-by":"publisher","first-page":"201","DOI":"10.1007\/s00401-019-01994-1","volume":"138","author":"A De Roeck","year":"2019","unstructured":"De Roeck A, Van Broeckhoven C, Sleegers K. The role of ABCA7 in Alzheimer\u2019s disease: evidence from genomics, transcriptomics and methylomics. Acta Neuropathologica. 2019;138:201\u201320.","journal-title":"Acta Neuropathologica"},{"key":"1235_CR50","doi-asserted-by":"publisher","first-page":"165","DOI":"10.1385\/IR:31:3:165","volume":"31","author":"P Iribarren","year":"2005","unstructured":"Iribarren P, Zhou Y, Hu J, Le Y, Wang JM. Role of formyl peptide receptor-like 1 (FPRL1\/FPR2) in mononuclear phagocyte responses in Alzheimer disease. Immunologic Res. 2005;31:165\u201376.","journal-title":"Immunologic Res"},{"key":"1235_CR51","doi-asserted-by":"publisher","first-page":"129","DOI":"10.1016\/j.neuroscience.2023.08.001","volume":"528","author":"L-L Lin","year":"2023","unstructured":"Lin L-L, Song GJ, Zhang H, Yin Y, Xin SM, Ding L, et al. GPR34 knockdown relieves cognitive deficits and suppresses neuroinflammation in Alzheimer\u2019s disease via the ERK\/NF-\u03baB signal. Neuroscience. 2023;528:129\u201339.","journal-title":"Neuroscience"},{"key":"1235_CR52","doi-asserted-by":"publisher","first-page":"2413","DOI":"10.1016\/j.neuron.2021.05.034","volume":"109","author":"Y Shi","year":"2021","unstructured":"Shi Y, Andhey PS, Ising C, Wang K, Snipes LL, Boyer K, et al. Overexpressing low-density lipoprotein receptor reduces tau-associated neurodegeneration in relation to apoE-linked mechanisms. Neuron. 2021;109:2413\u20132426.e7.","journal-title":"Neuron"},{"key":"1235_CR53","doi-asserted-by":"publisher","first-page":"683","DOI":"10.1038\/s41593-018-0120-6","volume":"21","author":"RA Hill","year":"2018","unstructured":"Hill RA, Li AM, Grutzendler J. Lifelong cortical myelin plasticity and age-related degeneration in the live mammalian brain. Nat Neurosci. 2018;21:683\u201395.","journal-title":"Nat Neurosci"},{"key":"1235_CR54","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1186\/s12974-019-1458-8","volume":"16","author":"A Sayo","year":"2019","unstructured":"Sayo A, Konishi H, Kobayashi M, Kano K, Kobayashi H, Hibi H, et al. GPR34 in spinal microglia exacerbates neuropathic pain in mice. J Neuroinflammation. 2019;16:1\u201311.","journal-title":"J Neuroinflammation"},{"key":"1235_CR55","doi-asserted-by":"publisher","first-page":"2292","DOI":"10.1016\/j.neuron.2021.05.012","volume":"109","author":"J-F Chen","year":"2021","unstructured":"Chen J-F, Liu K, Hu B, Li RR, Xin W, Chen H, et al. Enhancing myelin renewal reverses cognitive dysfunction in a murine model of Alzheimer\u2019s disease. Neuron. 2021;109:2292\u2013-2307.e5.","journal-title":"Neuron"},{"key":"1235_CR56","doi-asserted-by":"publisher","first-page":"358","DOI":"10.1038\/nrn3880","volume":"16","author":"FL Heppner","year":"2015","unstructured":"Heppner FL, Ransohoff RM, Becher B. Immune attack: the role of inflammation in Alzheimer disease. Nat Rev Neurosci. 2015;16:358\u201372.","journal-title":"Nat Rev Neurosci"},{"key":"1235_CR57","doi-asserted-by":"publisher","first-page":"669","DOI":"10.1038\/s41586-019-1769-z","volume":"575","author":"C Ising","year":"2019","unstructured":"Ising C, Venegas C, Zhang S, Scheiblich H, Schmidt SV, Vieira-Saecker A, et al. NLRP3 inflammasome activation drives tau pathology. Nature. 2019;575:669\u201373.","journal-title":"Nature"},{"key":"1235_CR58","doi-asserted-by":"publisher","first-page":"437","DOI":"10.1146\/annurev-med-050715-104343","volume":"69","author":"LI Labzin","year":"2018","unstructured":"Labzin LI, Heneka MT, Latz E. Innate Immunity and Neurodegeneration. Annu Rev Med. 2018;69:437\u201349.","journal-title":"Annu Rev Med"},{"key":"1235_CR59","doi-asserted-by":"publisher","first-page":"777","DOI":"10.1002\/glia.20477","volume":"55","author":"A B\u00e9dard","year":"2007","unstructured":"B\u00e9dard A, Tremblay P, Chernomoretz A, Valli\u00e8res L. Identification of genes preferentially expressed by microglia and upregulated during cuprizone-induced inflammation. Glia. 2007;55:777\u201389.","journal-title":"Glia"},{"key":"1235_CR60","doi-asserted-by":"publisher","first-page":"565","DOI":"10.1038\/s41582-019-0244-7","volume":"15","author":"Y Hou","year":"2019","unstructured":"Hou Y, Dan X, Babbar M, Wei Y, Hasselbalch SG, Croteau DL, et al. Aging as a risk factor for neurodegenerative disease. Nat Rev Neurol. 2019;15:565\u201381.","journal-title":"Nat Rev Neurol"},{"key":"1235_CR61","doi-asserted-by":"publisher","first-page":"995","DOI":"10.1038\/nn.4325","volume":"19","author":"S Safaiyan","year":"2016","unstructured":"Safaiyan S, Kannaiyan N, Snaidero N, Brioschi S, Biber K, Yona S, et al. Age-related myelin degradation burdens the clearance function of microglia during aging. Nat Neurosci. 2016;19:995\u20138.","journal-title":"Nat Neurosci"},{"key":"1235_CR62","doi-asserted-by":"publisher","first-page":"327","DOI":"10.1093\/jb\/mvt010","volume":"153","author":"K Makide","year":"2013","unstructured":"Makide K, Aoki J. GPR34 as a lysophosphatidylserine receptor. J Biochem. 2013;153:327\u20139.","journal-title":"J Biochem"},{"key":"1235_CR63","doi-asserted-by":"crossref","unstructured":"Izume, T, et al. Structural basis for lysophosphatidylserine recognition by GPR34. bioRxiv, 2023: 2023.02. 15.528751.","DOI":"10.1101\/2023.02.15.528751"},{"key":"1235_CR64","doi-asserted-by":"publisher","first-page":"279","DOI":"10.1016\/S1474-4422(02)00133-3","volume":"1","author":"PS Aisen","year":"2002","unstructured":"Aisen PS. The potential of anti-inflammatory drugs for the treatment of Alzheimer\u2019s disease. Lancet Neurol. 2002;1:279\u201384.","journal-title":"Lancet Neurol"},{"key":"1235_CR65","doi-asserted-by":"publisher","first-page":"2819","DOI":"10.1001\/jama.289.21.2819","volume":"289","author":"PS Aisen","year":"2003","unstructured":"Aisen PS, Schafer KA, Grundman M, Pfeiffer E, Sano M, Davis KL, et al. Effects of rofecoxib or naproxen vs placebo on Alzheimer disease progression: a randomized controlled trial. JAMA. 2003;289:2819\u201326.","journal-title":"JAMA"},{"key":"1235_CR66","doi-asserted-by":"publisher","first-page":"1023","DOI":"10.1016\/j.neuron.2018.01.031","volume":"97","author":"Y Zhao","year":"2018","unstructured":"Zhao Y, Wu X, Li X, Jiang LL, Gui X, Liu Y, et al. TREM2 is a receptor for beta-amyloid that mediates microglial function. Neuron. 2018;97:1023\u20131031.e7.","journal-title":"Neuron"},{"key":"1235_CR67","doi-asserted-by":"publisher","first-page":"631","DOI":"10.1016\/j.neuron.2013.04.014","volume":"78","author":"A Griciuc","year":"2013","unstructured":"Griciuc A, Serrano-Pozo A, Parrado AR, Lesinski AN, Asselin CN, Mullin K, et al. Alzheimer\u2019s disease risk gene CD33 inhibits microglial uptake of amyloid beta. Neuron. 2013;78:631\u201343.","journal-title":"Neuron"},{"key":"1235_CR68","doi-asserted-by":"publisher","first-page":"857","DOI":"10.1038\/ni.1636","volume":"9","author":"A Halle","year":"2008","unstructured":"Halle A, Hornung V, Petzold GC, Stewart CR, Monks BG, Reinheckel T, et al. The NALP3 inflammasome is involved in the innate immune response to amyloid-beta. Nat Immunol. 2008;9:857\u201365.","journal-title":"Nat Immunol"},{"key":"1235_CR69","doi-asserted-by":"publisher","first-page":"366","DOI":"10.1038\/ng1095","volume":"33","author":"C Lappe-Siefke","year":"2003","unstructured":"Lappe-Siefke C, Goebbels S, Gravel M, Nicksch E, Lee J, Braun PE, et al. Disruption of Cnp1 uncouples oligodendroglial functions in axonal support and myelination. Nat Genet. 2003;33:366\u201374.","journal-title":"Nat Genet"},{"key":"1235_CR70","doi-asserted-by":"publisher","first-page":"1123","DOI":"10.1016\/j.immuni.2021.05.007","volume":"54","author":"X Wang","year":"2021","unstructured":"Wang X, Cai J, Lin B, Ma M, Tao Y, Zhou Y, et al. GPR34-mediated sensing of lysophosphatidylserine released by apoptotic neutrophils activates type 3 innate lymphoid cells to mediate tissue repair. Immunity. 2021;54:1123\u20131136.e8.","journal-title":"Immunity"},{"key":"1235_CR71","doi-asserted-by":"publisher","first-page":"e9380","DOI":"10.1371\/journal.pone.0009380","volume":"5","author":"X Sun","year":"2010","unstructured":"Sun X, Wang X, Chen T, Li T, Cao K, Lu A, et al. Myelin activates FAK\/Akt\/NF-kappaB pathways and provokes CR3-dependent inflammatory response in murine system. PLoS One. 2010;5:e9380.","journal-title":"PLoS One"},{"key":"1235_CR72","doi-asserted-by":"crossref","unstructured":"Stine, WB, et al., Preparing synthetic A\u03b2 in different aggregation states, in Alzheimer\u2019s Disease and Frontotemporal Dementia. 2010, Springer. 13-32","DOI":"10.1007\/978-1-60761-744-0_2"},{"key":"1235_CR73","doi-asserted-by":"publisher","first-page":"1490","DOI":"10.1038\/nprot.2007.207","volume":"2","author":"GJ Brewer","year":"2007","unstructured":"Brewer GJ, Torricelli JR. Isolation and culture of adult neurons and neurospheres. Nat Protoc. 2007;2:1490\u20138.","journal-title":"Nat Protoc"},{"key":"1235_CR74","doi-asserted-by":"publisher","first-page":"193","DOI":"10.1186\/s40478-020-01061-x","volume":"8","author":"ACA Chiang","year":"2020","unstructured":"Chiang ACA, Seua AV, Singhmar P, Arroyo LD, Mahalingam R, Hu J, et al. Bexarotene normalizes chemotherapy-induced myelin decompaction and reverses cognitive and sensorimotor deficits in mice. Acta Neuropathol Commun. 2020;8:193.","journal-title":"Acta Neuropathol Commun"},{"key":"1235_CR75","doi-asserted-by":"publisher","first-page":"e2308435120","DOI":"10.1073\/pnas.2308435120","volume":"120","author":"A Xia","year":"2023","unstructured":"Xia A, Yong X, Zhang C, Lin G, Jia G, Zhao C, et al. Cryo-EM structures of human GPR34 enable the identification of selective antagonists. Proc Natl Acad Sci. 2023;120:e2308435120.","journal-title":"Proc Natl Acad Sci"},{"key":"1235_CR76","doi-asserted-by":"publisher","first-page":"2203","DOI":"10.3390\/cells12172203","volume":"12","author":"M Cammarota","year":"2023","unstructured":"Cammarota M, Boscia F. Contribution of oligodendrocytes, microglia, and astrocytes to myelin debris uptake in an explant model of inflammatory demyelination in rats. Cells. 2023;12:2203.","journal-title":"Cells"}],"container-title":["Cellular & Molecular Immunology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.nature.com\/articles\/s41423-024-01235-w.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/s41423-024-01235-w","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/s41423-024-01235-w.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,3,28]],"date-time":"2025-03-28T17:36:58Z","timestamp":1743183418000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.nature.com\/articles\/s41423-024-01235-w"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,1,1]]},"references-count":76,"journal-issue":{"issue":"2","published-online":{"date-parts":[[2025,2]]}},"alternative-id":["1235"],"URL":"https:\/\/doi.org\/10.1038\/s41423-024-01235-w","relation":{},"ISSN":["2042-0226"],"issn-type":[{"value":"2042-0226","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,1,1]]},"assertion":[{"value":"8 July 2024","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"22 October 2024","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"1 January 2025","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"BL, WJ and RZ are co-inventors of a pending patent application (202110355421.6) submitted by University of Science and Technology of China. All the other authors declare that they have no competing interests. RZ is Deputy Editor-in-Chief of Cellular & Molecular Immunology, but he has not been involved in the peer review or the decision-making of the article.","order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}]}}