{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,29]],"date-time":"2026-10-29T19:03:30Z","timestamp":1793300610051,"version":"4.5.0"},"reference-count":61,"publisher":"Springer Science and Business Media LLC","issue":"6","license":[{"start":{"date-parts":[[2021,5,6]],"date-time":"2021-05-06T00:00:00Z","timestamp":1620259200000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.springer.com\/tdm"},{"start":{"date-parts":[[2021,5,6]],"date-time":"2021-05-06T00:00:00Z","timestamp":1620259200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/www.springer.com\/tdm"}],"funder":[{"DOI":"10.13039\/100000049","name":"U.S. Department of Health & Human Services | NIH | National Institute on Aging","doi-asserted-by":"publisher","award":["R01AG048017"],"award-info":[{"award-number":["R01AG048017"]}],"id":[{"id":"10.13039\/100000049","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000049","name":"U.S. Department of Health & Human Services | NIH | National Institute on Aging","doi-asserted-by":"publisher","award":["RF1AG055421"],"award-info":[{"award-number":["RF1AG055421"]}],"id":[{"id":"10.13039\/100000049","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000049","name":"U.S. Department of Health & Human Services | NIH | National Institute on Aging","doi-asserted-by":"publisher","award":["R01AG055682"],"award-info":[{"award-number":["R01AG055682"]}],"id":[{"id":"10.13039\/100000049","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Nat Neurosci"],"published-print":{"date-parts":[[2021,6]]},"DOI":"10.1038\/s41593-021-00851-3","type":"journal-article","created":{"date-parts":[[2021,5,6]],"date-time":"2021-05-06T12:03:37Z","timestamp":1620302617000},"page":"786-798","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":185,"title":["Neuronal ApoE upregulates MHC-I expression to drive selective neurodegeneration in Alzheimer\u2019s disease"],"prefix":"10.1038","volume":"24","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-1895-2654","authenticated-orcid":false,"given":"Kelly A.","family":"Zalocusky","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ramsey","family":"Najm","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alice L.","family":"Taubes","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yanxia","family":"Hao","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Seo Yeon","family":"Yoon","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2761-1480","authenticated-orcid":false,"given":"Nicole","family":"Koutsodendris","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1990-5099","authenticated-orcid":false,"given":"Maxine R.","family":"Nelson","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Antara","family":"Rao","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David A.","family":"Bennett","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jason","family":"Bant","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dah-eun J.","family":"Amornkul","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qin","family":"Xu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alice","family":"An","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Olga","family":"Cisne-Thomson","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":"297","published-online":{"date-parts":[[2021,5,6]]},"reference":[{"key":"851_CR1","doi-asserted-by":"publisher","first-page":"1350","DOI":"10.1038\/s41593-018-0221-2","volume":"21","author":"H Fu","year":"2018","unstructured":"Fu, H., Hardy, J. & Duff, K. E. Selective vulnerability in neurodegenerative diseases. Nat. Neurosci. 21, 1350\u20131358 (2018).","journal-title":"Nat. Neurosci."},{"key":"851_CR2","doi-asserted-by":"publisher","first-page":"13707","DOI":"10.1523\/JNEUROSCI.4040-10.2010","volume":"30","author":"Y Andrews-Zwilling","year":"2010","unstructured":"Andrews-Zwilling, Y. et al. Apolipoprotein E4 causes age- and tau-dependent impairment of GABAergic interneurons, leading to learning and memory deficits in mice. J. Neurosci. 30, 13707\u201313717 (2010).","journal-title":"J. Neurosci."},{"key":"851_CR3","doi-asserted-by":"publisher","first-page":"1204","DOI":"10.1016\/j.cell.2012.02.040","volume":"148","author":"Y Huang","year":"2012","unstructured":"Huang, Y. & Mucke, L. Alzheimer mechanisms and therapeutic strategies. Cell 148, 1204\u20131222 (2012).","journal-title":"Cell"},{"key":"851_CR4","doi-asserted-by":"crossref","unstructured":"Najm, R., Jones, E. A. & Huang, Y. Apolipoprotein E4, inhibitory network dysfunction, and Alzheimer\u2019s disease. Mol. Neurodegener. 14, 24 (2019).","DOI":"10.1186\/s13024-019-0324-6"},{"key":"851_CR5","doi-asserted-by":"publisher","first-page":"1349","DOI":"10.1001\/jama.1997.03550160069041","volume":"278","author":"LA Farrer","year":"1997","unstructured":"Farrer, L. A. et al. Effects of age, sex, and ethnicity on the association between apolipoprotein E genotype and Alzheimer disease: a meta-analysis. JAMA 278, 1349\u20131356 (1997).","journal-title":"JAMA"},{"key":"851_CR6","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1159\/000334607","volume":"38","author":"A Ward","year":"2012","unstructured":"Ward, A. et al. Prevalence of apolipoprotein E4 genotype and homozygotes (APOE e4\/4) among patients diagnosed with Alzheimer\u2019s disease: a systematic review and meta-analysis. Neuroepidemiology 38, 1\u201317 (2012).","journal-title":"Neuroepidemiology"},{"key":"851_CR7","doi-asserted-by":"publisher","first-page":"148","DOI":"10.1016\/0005-2760(87)90295-5","volume":"917","author":"RE Pitas","year":"1987","unstructured":"Pitas, R. E., Boyles, J. K., Lee, S. H., Foss, D. & Mahley, R. W. Astrocytes synthesize apolipoprotein E and metabolize apolipoprotein E-containing lipoproteins. Biochim. Biophys. Acta 917, 148\u2013161 (1987).","journal-title":"Biochim. Biophys. Acta"},{"key":"851_CR8","doi-asserted-by":"publisher","first-page":"647","DOI":"10.1038\/s41591-018-0004-z","volume":"24","author":"C Wang","year":"2018","unstructured":"Wang, C. et al. Gain of toxic apolipoprotein E4 effects in human iPSC-derived neurons is ameliorated by a small-molecule structure corrector. Nat. Med. 24, 647\u2013657 (2018).","journal-title":"Nat. Med."},{"key":"851_CR9","doi-asserted-by":"publisher","first-page":"601","DOI":"10.1016\/S0002-9440(10)65305-9","volume":"154","author":"P-T Xu","year":"1999","unstructured":"Xu, P.-T. et al. Specific regional transcription of apolipoprotein E in human brain neurons. Am. J. Pathol. 154, 601\u2013611 (1999).","journal-title":"Am. J. Pathol."},{"key":"851_CR10","doi-asserted-by":"publisher","first-page":"4985","DOI":"10.1523\/JNEUROSCI.5476-05.2006","volume":"26","author":"Q Xu","year":"2006","unstructured":"Xu, Q. et al. Profile and regulation of apolipoprotein E (apoE) expression in the CNS in mice with targeting of green fluorescent protein gene to the apoE locus. J. Neurosci. 26, 4985\u20134994 (2006).","journal-title":"J. Neurosci."},{"key":"851_CR11","doi-asserted-by":"publisher","first-page":"14069","DOI":"10.1523\/JNEUROSCI.2281-14.2014","volume":"34","author":"J Knoferle","year":"2014","unstructured":"Knoferle, J. et al. Apolipoprotein E4 produced in GABAergic interneurons causes learning and memory deficits in mice. J. Neurosci. 34, 14069\u201314078 (2014).","journal-title":"J. Neurosci."},{"key":"851_CR12","doi-asserted-by":"publisher","first-page":"17217","DOI":"10.1074\/jbc.M110.217380","volume":"286","author":"J Brodbeck","year":"2011","unstructured":"Brodbeck, J. et al. Structure-dependent impairment of intracellular apolipoprotein E4 trafficking and its detrimental effects are rescued by small-molecule structure correctors. J. Biol. Chem. 286, 17217\u201317226 (2011).","journal-title":"J. Biol. Chem."},{"key":"851_CR13","doi-asserted-by":"publisher","first-page":"1141","DOI":"10.1016\/j.neuron.2018.05.008","volume":"98","author":"Y-T Lin","year":"2018","unstructured":"Lin, Y.-T. et al. APOE4 causes widespread molecular and cellular alterations associated with Alzheimer\u2019s disease phenotypes in human iPSC-derived brain cell types. Neuron 98, 1141\u20131154 (2018).","journal-title":"Neuron"},{"key":"851_CR14","doi-asserted-by":"publisher","first-page":"523","DOI":"10.1038\/nature24016","volume":"549","author":"Y Shi","year":"2017","unstructured":"Shi, Y. et al. ApoE4 markedly exacerbates tau-mediated neurodegeneration in a mouse model of tauopathy. Nature 549, 523\u2013527 (2017).","journal-title":"Nature"},{"key":"851_CR15","doi-asserted-by":"publisher","first-page":"991","DOI":"10.3233\/JAD-181184","volume":"68","author":"AL Orr","year":"2019","unstructured":"Orr, A. L. et al. Neuronal apolipoprotein E4 expression results in proteome-wide alterations and compromises bioenergetic capacity by disrupting mitochondrial function. J. Alzheimers Dis. 68, 991\u20131011 (2019).","journal-title":"J. Alzheimers Dis."},{"key":"851_CR16","doi-asserted-by":"publisher","first-page":"5644","DOI":"10.1073\/pnas.0600549103","volume":"103","author":"RW Mahley","year":"2006","unstructured":"Mahley, R. W., Weisgraber, K. H. & Huang, Y. Apolipoprotein E4: a causative factor and therapeutic target in neuropathology, including Alzheimer\u2019s disease. Proc. Natl Acad. Sci. USA 103, 5644\u20135651 (2006).","journal-title":"Proc. Natl Acad. Sci. USA"},{"key":"851_CR17","doi-asserted-by":"publisher","first-page":"1100","DOI":"10.1016\/j.neuron.2012.01.020","volume":"73","author":"JD Adelson","year":"2012","unstructured":"Adelson, J. D. et al. Neuroprotection from stroke in the absence of MHCI or PirB. Neuron 73, 1100\u20131107 (2012).","journal-title":"Neuron"},{"key":"851_CR18","doi-asserted-by":"publisher","first-page":"e0161463","DOI":"10.1371\/journal.pone.0161463","volume":"11","author":"AL Bombeiro","year":"2016","unstructured":"Bombeiro, A. L. et al. MHC-I and PirB upregulation in the central and peripheral nervous system following sciatic nerve injury. PLoS ONE 11, e0161463 (2016).","journal-title":"PLoS ONE"},{"key":"851_CR19","doi-asserted-by":"publisher","first-page":"505","DOI":"10.1016\/S0896-6273(00)80562-0","volume":"21","author":"RA Corriveau","year":"1998","unstructured":"Corriveau, R. A., Huh, G. S. & Shatz, C. J. Regulation of class I MHC gene expression in the developing and mature CNS by neural activity. Neuron 21, 505\u2013520 (1998).","journal-title":"Neuron"},{"key":"851_CR20","doi-asserted-by":"publisher","first-page":"16","DOI":"10.1093\/gerona\/glv232","volume":"72","author":"CA Mangold","year":"2017","unstructured":"Mangold, C. A. et al. CNS-wide sexually dimorphic induction of the major histocompatibility complex 1 pathway with aging. J. Gerontol. A Biol. Sci. Med. Sci. 72, 16\u201329 (2017).","journal-title":"J. Gerontol. A Biol. Sci. Med. Sci."},{"key":"851_CR21","doi-asserted-by":"publisher","first-page":"111","DOI":"10.1007\/s12031-012-9783-8","volume":"48","author":"HDV Starkey","year":"2012","unstructured":"Starkey, H. D. V. et al. Neuroglial expression of the MHCI pathway and PirB receptor is upregulated in the hippocampus with advanced aging. J. Mol. Neurosci. 48, 111\u2013126 (2012).","journal-title":"J. Mol. Neurosci."},{"key":"851_CR22","doi-asserted-by":"publisher","first-page":"463","DOI":"10.1016\/j.neuron.2009.10.015","volume":"64","author":"A Datwani","year":"2009","unstructured":"Datwani, A. et al. Classical MHCI molecules regulate retinogeniculate refinement and limit ocular dominance plasticity. Neuron 64, 463\u2013470 (2009).","journal-title":"Neuron"},{"key":"851_CR23","doi-asserted-by":"publisher","first-page":"195","DOI":"10.1038\/nature13154","volume":"509","author":"H Lee","year":"2014","unstructured":"Lee, H. et al. Synapse elimination and learning rules co-regulated by MHC class I H2-Db. Nature 509, 195\u2013200 (2014).","journal-title":"Nature"},{"key":"851_CR24","doi-asserted-by":"publisher","first-page":"e53569","DOI":"10.1371\/journal.pone.0053569","volume":"7","author":"L Leung","year":"2012","unstructured":"Leung, L. et al. Apolipoprotein E4 causes age- and sex-dependent impairments of hilar GABAergic interneurons and learning and memory deficits in mice. PLoS ONE 7, e53569 (2012).","journal-title":"PLoS ONE"},{"key":"851_CR25","doi-asserted-by":"publisher","first-page":"11929","DOI":"10.1523\/JNEUROSCI.1860-14.2014","volume":"34","author":"Y Zhang","year":"2014","unstructured":"Zhang, Y. et al. An RNA-sequencing transcriptome and splicing database of glia, neurons, and vascular cells of the cerebral cortex. J. Neurosci. 34, 11929\u201311947 (2014).","journal-title":"J. Neurosci."},{"key":"851_CR26","doi-asserted-by":"publisher","first-page":"e14997","DOI":"10.7554\/eLife.14997","volume":"5","author":"MS Cembrowski","year":"2016","unstructured":"Cembrowski, M. S., Wang, L., Sugino, K., Shields, B. C. & Spruston, N. Hipposeq: a comprehensive RNA-seq database of gene expression in hippocampal principal neurons. eLife 5, e14997 (2016).","journal-title":"eLife"},{"key":"851_CR27","doi-asserted-by":"publisher","first-page":"1015","DOI":"10.1016\/j.cell.2018.07.028","volume":"174","author":"A Saunders","year":"2018","unstructured":"Saunders, A. et al. Molecular diversity and specializations among the cells of the adult mouse brain. Cell 174, 1015\u20131030 (2018).","journal-title":"Cell"},{"key":"851_CR28","doi-asserted-by":"publisher","first-page":"168","DOI":"10.1038\/nature05453","volume":"445","author":"ES Lein","year":"2007","unstructured":"Lein, E. S. et al. Genome-wide atlas of gene expression in the adult mouse brain. Nature 445, 168\u2013176 (2007).","journal-title":"Nature"},{"key":"851_CR29","doi-asserted-by":"publisher","first-page":"716","DOI":"10.1016\/j.cell.2018.05.061","volume":"174","author":"Dvan Dijk","year":"2018","unstructured":"Dijk, Dvan et al. Recovering gene interactions from single-cell data using data diffusion. Cell 174, 716\u2013729 (2018).","journal-title":"Cell"},{"key":"851_CR30","doi-asserted-by":"publisher","first-page":"27","DOI":"10.1093\/nar\/28.1.27","volume":"28","author":"M Kanehisa","year":"2000","unstructured":"Kanehisa, M. & Goto, S. KEGG: Kyoto Encyclopedia of Genes and Genomes. Nucleic Acids Res. 28, 27\u201330 (2000).","journal-title":"Nucleic Acids Res."},{"key":"851_CR31","doi-asserted-by":"publisher","first-page":"613","DOI":"10.1038\/nn.3356","volume":"16","author":"E Suberbielle","year":"2013","unstructured":"Suberbielle, E. et al. Physiologic brain activity causes DNA double-strand breaks in neurons, with exacerbation by amyloid-\u03b2. Nat. Neurosci. 16, 613\u2013621 (2013).","journal-title":"Nat. Neurosci."},{"key":"851_CR32","doi-asserted-by":"publisher","first-page":"162","DOI":"10.1016\/j.neurobiolaging.2017.09.012","volume":"63","author":"Y Gerakis","year":"2018","unstructured":"Gerakis, Y. & Hetz, C. A decay of the adaptive capacity of the unfolded protein response exacerbates Alzheimer\u2019s disease. Neurobiol. Aging 63, 162\u2013164 (2018).","journal-title":"Neurobiol. Aging"},{"key":"851_CR33","doi-asserted-by":"publisher","first-page":"759","DOI":"10.1038\/s41577-018-0051-1","volume":"18","author":"Y Shi","year":"2018","unstructured":"Shi, Y. & Holtzman, D. M. Interplay between innate immunity and Alzheimer disease: APOE and TREM2 in the spotlight. Nat. Rev. Immunol. 18, 759 (2018).","journal-title":"Nat. Rev. Immunol."},{"key":"851_CR34","doi-asserted-by":"publisher","first-page":"72","DOI":"10.1038\/s41586-018-0654-5","volume":"563","author":"B Tasic","year":"2018","unstructured":"Tasic, B. et al. Shared and distinct transcriptomic cell types across neocortical areas. Nature 563, 72\u201378 (2018).","journal-title":"Nature"},{"key":"851_CR35","doi-asserted-by":"publisher","first-page":"332","DOI":"10.1038\/s41586-019-1195-2","volume":"570","author":"H Mathys","year":"2019","unstructured":"Mathys, H. et al. Single-cell transcriptomic analysis of Alzheimer\u2019s disease. Nature 570, 332\u2013337 (2019).","journal-title":"Nature"},{"key":"851_CR36","doi-asserted-by":"publisher","first-page":"7285","DOI":"10.1073\/pnas.1507125112","volume":"112","author":"S Darmanis","year":"2015","unstructured":"Darmanis, S. et al. A survey of human brain transcriptome diversity at the single cell level. Proc. Natl Acad. Sci. USA 112, 7285\u20137290 (2015).","journal-title":"Proc. Natl Acad. Sci. USA"},{"key":"851_CR37","doi-asserted-by":"publisher","DOI":"10.1186\/1471-2164-9-178","volume":"9","author":"M Ohtsuka","year":"2008","unstructured":"Ohtsuka, M., Inoko, H., Kulski, J. K. & Yoshimura, S. Major histocompatibility complex (Mhc) class Ib gene duplications, organization and expression patterns in mouse strain C57BL\/6. BMC Genomics 9, 178 (2008).","journal-title":"BMC Genomics"},{"key":"851_CR38","doi-asserted-by":"publisher","first-page":"2527","DOI":"10.1523\/JNEUROSCI.4315-03.2004","volume":"24","author":"WJ Brecht","year":"2004","unstructured":"Brecht, W. J. et al. Neuron-specific apolipoprotein E4 proteolysis is associated with increased tau phosphorylation in brains of transgenic mice. J. Neurosci. 24, 2527\u20132534 (2004).","journal-title":"J. Neurosci."},{"key":"851_CR39","doi-asserted-by":"publisher","first-page":"121","DOI":"10.1111\/nan.12084","volume":"40","author":"S Mondrag\u00f3n\u2010Rodr\u00edguez","year":"2014","unstructured":"Mondrag\u00f3n\u2010Rodr\u00edguez, S., Perry, G., Luna\u2010Mu\u00f1oz, J., Acevedo\u2010Aquino, M. C. & Williams, S. Phosphorylation of tau protein at sites Ser396\u2013404 is one of the earliest events in Alzheimer\u2019s disease and Down syndrome. Neuropathol. Appl. Neurobiol. 40, 121\u2013135 (2014).","journal-title":"Neuropathol. Appl. Neurobiol."},{"key":"851_CR40","doi-asserted-by":"publisher","first-page":"239","DOI":"10.1007\/BF00308809","volume":"82","author":"H Braak","year":"1991","unstructured":"Braak, H. & Braak, E. Neuropathological stageing of Alzheimer-related changes. Acta Neuropathol. 82, 239\u2013259 (1991).","journal-title":"Acta Neuropathol."},{"key":"851_CR41","doi-asserted-by":"publisher","first-page":"663","DOI":"10.1038\/nrn2194","volume":"8","author":"C Ballatore","year":"2007","unstructured":"Ballatore, C., Lee, V. M.-Y. & Trojanowski, J. Q. Tau-mediated neurodegeneration in Alzheimer\u2019s disease and related disorders. Nat. Rev. Neurosci. 8, 663\u2013672 (2007).","journal-title":"Nat. Rev. Neurosci."},{"key":"851_CR42","doi-asserted-by":"publisher","first-page":"403","DOI":"10.1146\/annurev.iy.11.040193.002155","volume":"11","author":"RN Germain","year":"1993","unstructured":"Germain, R. N. & Margulies, D. H. The biochemistry and cell biology of antigen processing and presentation. Ann. Rev. Immunol. 11, 403\u2013450 (1993).","journal-title":"Ann. Rev. Immunol."},{"key":"851_CR43","doi-asserted-by":"crossref","unstructured":"Hansen, T. H. & Leet, D. R. Mechanism of class I assembly with \u03b22 microglobulin and loading with peptide. In: Advances in Immunology (ed Dixon, F. J.) 64, 105\u2013137 (Academic Press, 1997).","DOI":"10.1016\/S0065-2776(08)60888-3"},{"key":"851_CR44","doi-asserted-by":"publisher","first-page":"10966","DOI":"10.1073\/pnas.1434398100","volume":"100","author":"FM Harris","year":"2003","unstructured":"Harris, F. M. et al. Carboxyl-terminal-truncated apolipoprotein E4 causes Alzheimer\u2019s disease-like neurodegeneration and behavioral deficits in transgenic mice. Proc. Natl Acad. Sci. USA 100, 10966\u201310971 (2003).","journal-title":"Proc. Natl Acad. Sci. USA"},{"key":"851_CR45","doi-asserted-by":"publisher","first-page":"951","DOI":"10.1016\/S0002-9440(10)64963-2","volume":"156","author":"I Tesseur","year":"2000","unstructured":"Tesseur, I. et al. Expression of human apolipoprotein E4 in neurons causes hyperphosphorylation of protein tau in the brains of transgenic mice. Am. J. Pathol. 156, 951\u2013964 (2000).","journal-title":"Am. J. Pathol."},{"key":"851_CR46","doi-asserted-by":"publisher","first-page":"6828","DOI":"10.1073\/pnas.0702023104","volume":"104","author":"CA Goddard","year":"2007","unstructured":"Goddard, C. A., Butts, D. A. & Shatz, C. J. Regulation of CNS synapses by neuronal MHC class I. Proc. Natl Acad. Sci. USA 104, 6828\u20136833 (2007).","journal-title":"Proc. Natl Acad. Sci. USA"},{"key":"851_CR47","doi-asserted-by":"publisher","first-page":"399","DOI":"10.1038\/s41586-019-1895-7","volume":"577","author":"D Gate","year":"2020","unstructured":"Gate, D. et al. Clonally expanded CD8 T cells patrol the cerebrospinal fluid in Alzheimer\u2019s disease. Nature 577, 399\u2013404 (2020).","journal-title":"Nature"},{"key":"851_CR48","doi-asserted-by":"publisher","first-page":"2155","DOI":"10.1126\/science.290.5499.2155","volume":"290","author":"GS Huh","year":"2000","unstructured":"Huh, G. S. et al. Functional requirement for class I MHC in CNS development and plasticity. Science 290, 2155\u20132159 (2000).","journal-title":"Science"},{"key":"851_CR49","doi-asserted-by":"publisher","first-page":"1399","DOI":"10.1126\/science.1242077","volume":"341","author":"T Kim","year":"2013","unstructured":"Kim, T. et al. Human LilrB2 is a \u03b2-amyloid receptor and its murine homolog PirB regulates synaptic plasticity in an Alzheimer\u2019s model. Science 341, 1399\u20131404 (2013).","journal-title":"Science"},{"key":"851_CR50","doi-asserted-by":"publisher","first-page":"209","DOI":"10.1038\/nrn3710","volume":"15","author":"GC Brown","year":"2014","unstructured":"Brown, G. C. & Neher, J. J. Microglial phagocytosis of live neurons. Nat. Rev. Neurosci. 15, 209\u2013216 (2014).","journal-title":"Nat. Rev. Neurosci."},{"key":"851_CR51","doi-asserted-by":"publisher","first-page":"353","DOI":"10.1093\/hmg\/9.3.353","volume":"9","author":"H Hamanaka","year":"2000","unstructured":"Hamanaka, H. et al. Altered cholesterol metabolism in human apolipoprotein E4 knock-in mice. Hum. Mol. Genet. 9, 353\u2013361 (2000).","journal-title":"Hum. Mol. Genet."},{"key":"851_CR52","doi-asserted-by":"publisher","first-page":"4803","DOI":"10.1523\/JNEUROSCI.0033-12.2012","volume":"32","author":"N Bien-Ly","year":"2012","unstructured":"Bien-Ly, N., Gillespie, A. K., Walker, D., Yoon, S. Y. & Huang, Y. Reducing human apolipoprotein E levels attenuates age-dependent A\u03b2 accumulation in mutant human amyloid precursor protein transgenic mice. J. Neurosci. 32, 4803\u20134811 (2012).","journal-title":"J. Neurosci."},{"key":"851_CR53","doi-asserted-by":"publisher","first-page":"S161","DOI":"10.3233\/JAD-179939","volume":"64","author":"DA Bennett","year":"2018","unstructured":"Bennett, D. A. et al. Religious Orders Study and Rush Memory and Aging Project. J. Alzheimers Dis. 64, S161\u2013S189 (2018).","journal-title":"J. Alzheimers Dis."},{"key":"851_CR54","doi-asserted-by":"publisher","DOI":"10.1038\/sdata.2018.142","volume":"5","author":"PL De Jager","year":"2018","unstructured":"De Jager, P. L. et al. A multi-omic atlas of the human frontal cortex for aging and Alzheimer\u2019s disease research. Sci. Data 5, 180142 (2018).","journal-title":"Sci. Data"},{"key":"851_CR55","unstructured":"10x Genomics. Sample Preparation Demonstrated Protocols: Isolation of Nuclei for Single Cell RNA Sequencing https:\/\/assets.ctfassets.net\/an68im79xiti\/6FhJX6yndYy0OwskGmMc8I\/e2677be827e82cd954ecfb8b30278e5e\/CG000124_SamplePrepDemonstratedProtocol_-_Nuclei_RevD.pdf (2018)."},{"key":"851_CR56","unstructured":"Allen Institute for Brain Science. Allen Cell Types Database Technical White Paper: Transcriptomics. http:\/\/help.brain-map.org\/download\/attachments\/8323525\/CellTypes_Transcriptomics_Overview.pdf?version=4&modificationDate=1538066831541&api=v2 (2018)."},{"key":"851_CR57","doi-asserted-by":"publisher","first-page":"411","DOI":"10.1038\/nbt.4096","volume":"36","author":"A Butler","year":"2018","unstructured":"Butler, A., Hoffman, P., Smibert, P., Papalexi, E. & Satija, R. Integrating single-cell transcriptomic data across different conditions, technologies, and species. Nat. Biotechnol. 36, 411\u2013420 (2018).","journal-title":"Nat. Biotechnol."},{"key":"851_CR58","doi-asserted-by":"publisher","first-page":"1888","DOI":"10.1016\/j.cell.2019.05.031","volume":"177","author":"T Stuart","year":"2019","unstructured":"Stuart, T. et al. Comprehensive integration of single-cell data. Cell 177, 1888\u20131902 (2019).","journal-title":"Cell"},{"key":"851_CR59","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1093\/nar\/gkv007","volume":"43","author":"ME Ritchie","year":"2015","unstructured":"Ritchie, M. E. et al. limma powers differential expression analyses for RNA-sequencing and microarray studies. Nucleic Acids Res. 43, 1\u201313 (2015). e47.","journal-title":"Nucleic Acids Res."},{"key":"851_CR60","doi-asserted-by":"publisher","first-page":"2498","DOI":"10.1101\/gr.1239303","volume":"13","author":"P Shannon","year":"2003","unstructured":"Shannon, P. et al. Cytoscape: a software environment for integrated models of biomolecular interaction networks. Genome Res. 13, 2498\u20132504 (2003).","journal-title":"Genome Res."},{"key":"851_CR61","doi-asserted-by":"publisher","first-page":"886","DOI":"10.1038\/nn.4548","volume":"20","author":"Z He","year":"2017","unstructured":"He, Z. et al. Comprehensive transcriptome analysis of neocortical layers in humans, chimpanzees and macaques. Nat. Neurosci. 20, 886\u2013895 (2017).","journal-title":"Nat. Neurosci."}],"container-title":["Nature Neuroscience"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.nature.com\/articles\/s41593-021-00851-3.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/s41593-021-00851-3","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/s41593-021-00851-3.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,10,29]],"date-time":"2022-10-29T18:04:23Z","timestamp":1667066663000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.nature.com\/articles\/s41593-021-00851-3"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,5,6]]},"references-count":61,"journal-issue":{"issue":"6","published-print":{"date-parts":[[2021,6]]}},"alternative-id":["851"],"URL":"https:\/\/doi.org\/10.1038\/s41593-021-00851-3","relation":{"has-review":[{"id-type":"doi","id":"10.3410\/f.740066834.793585890","asserted-by":"object"}]},"ISSN":["1097-6256","1546-1726"],"issn-type":[{"value":"1097-6256","type":"print"},{"value":"1546-1726","type":"electronic"}],"subject":[],"published":{"date-parts":[[2021,5,6]]},"assertion":[{"value":"9 November 2020","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"30 March 2021","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"6 May 2021","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"Y. Huang is a co-founder and scientific advisory board member of E-Scape Bio, GABAeron and Mederon Bio. All other authors declare no competing financial interests.","order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}]}}