{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,12]],"date-time":"2026-02-12T15:31:33Z","timestamp":1770910293486,"version":"3.50.1"},"reference-count":26,"publisher":"Springer Science and Business Media LLC","issue":"2","license":[{"start":{"date-parts":[[2026,1,26]],"date-time":"2026-01-26T00:00:00Z","timestamp":1769385600000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.springernature.com\/gp\/researchers\/text-and-data-mining"},{"start":{"date-parts":[[2026,1,26]],"date-time":"2026-01-26T00:00:00Z","timestamp":1769385600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/www.springernature.com\/gp\/researchers\/text-and-data-mining"}],"funder":[{"DOI":"10.13039\/100005440","name":"U.S. Department of Health & Human Services | NIH | Center for Scientific Review","doi-asserted-by":"publisher","award":["RF1AG082339"],"award-info":[{"award-number":["RF1AG082339"]}],"id":[{"id":"10.13039\/100005440","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100005440","name":"U.S. Department of Health & Human Services | NIH | Center for Scientific Review","doi-asserted-by":"publisher","award":["F30NS124136"],"award-info":[{"award-number":["F30NS124136"]}],"id":[{"id":"10.13039\/100005440","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100005440","name":"U.S. Department of Health & Human Services | NIH | Center for Scientific Review","doi-asserted-by":"publisher","award":["RF1AG082339"],"award-info":[{"award-number":["RF1AG082339"]}],"id":[{"id":"10.13039\/100005440","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100005440","name":"U.S. Department of Health & Human Services | NIH | Center for Scientific Review","doi-asserted-by":"publisher","award":["RF1AG082339"],"award-info":[{"award-number":["RF1AG082339"]}],"id":[{"id":"10.13039\/100005440","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100005440","name":"U.S. Department of Health & Human Services | NIH | Center for Scientific Review","doi-asserted-by":"publisher","award":["R01AG082730"],"award-info":[{"award-number":["R01AG082730"]}],"id":[{"id":"10.13039\/100005440","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100005440","name":"U.S. Department of Health & Human Services | NIH | Center for Scientific Review","doi-asserted-by":"publisher","award":["R01AG082730"],"award-info":[{"award-number":["R01AG082730"]}],"id":[{"id":"10.13039\/100005440","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100005440","name":"U.S. Department of Health & Human Services | NIH | Center for Scientific Review","doi-asserted-by":"publisher","award":["P30AG072946"],"award-info":[{"award-number":["P30AG072946"]}],"id":[{"id":"10.13039\/100005440","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000957","name":"Alzheimer's Association","doi-asserted-by":"publisher","award":["ABA-25-1376140, ABA-22-972169-Invite, ABA-22-972169"],"award-info":[{"award-number":["ABA-25-1376140, ABA-22-972169-Invite, ABA-22-972169"]}],"id":[{"id":"10.13039\/100000957","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000957","name":"Alzheimer's Association","doi-asserted-by":"publisher","award":["2019-AARG-644082"],"award-info":[{"award-number":["2019-AARG-644082"]}],"id":[{"id":"10.13039\/100000957","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100006312","name":"BrightFocus Foundation","doi-asserted-by":"publisher","award":["A2020161S"],"award-info":[{"award-number":["A2020161S"]}],"id":[{"id":"10.13039\/100006312","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Nat Genet"],"published-print":{"date-parts":[[2026,2]]},"DOI":"10.1038\/s41588-025-02473-y","type":"journal-article","created":{"date-parts":[[2026,1,26]],"date-time":"2026-01-26T10:02:32Z","timestamp":1769421752000},"page":"273-274","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Reply to: a quantitative trait locus for reduced microglial APOE expression associates with reduced cerebral amyloid angiopathy"],"prefix":"10.1038","volume":"58","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-6093-4823","authenticated-orcid":false,"given":"Lincoln M. P.","family":"Shade","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1240-0506","authenticated-orcid":false,"given":"Qi","family":"Qiao","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0188-8094","authenticated-orcid":false,"given":"Yuriko","family":"Katsumata","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2522-2884","authenticated-orcid":false,"given":"Shubhabrata","family":"Mukherjee","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7638-0749","authenticated-orcid":false,"given":"Jai G.","family":"Broome","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Lance A.","family":"Johnson","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9158-4440","authenticated-orcid":false,"given":"Mark T. W.","family":"Ebbert","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Peter T.","family":"Nelson","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7207-4696","authenticated-orcid":false,"given":"David W.","family":"Fardo","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"297","published-online":{"date-parts":[[2026,1,26]]},"reference":[{"key":"2473_CR1","doi-asserted-by":"publisher","first-page":"2407","DOI":"10.1038\/s41588-024-01939-9","volume":"56","author":"LMP Shade","year":"2024","unstructured":"Shade, L. M. P. et al. GWAS of multiple neuropathology endophenotypes identifies new risk loci and provides insights into the genetic risk of dementia. Nat. Genet. 56, 2407\u20132421 (2024).","journal-title":"Nat. Genet."},{"key":"2473_CR2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pgen.1004383","volume":"10","author":"C Giambartolomei","year":"2014","unstructured":"Giambartolomei, C. et al. Bayesian test for colocalisation between pairs of genetic association studies using summary statistics. PLoS Genet. 10, e1004383 (2014).","journal-title":"PLoS Genet."},{"key":"2473_CR3","doi-asserted-by":"publisher","first-page":"708","DOI":"10.1097\/NEN.0b013e31829a25b9","volume":"72","author":"PT Nelson","year":"2013","unstructured":"Nelson, P. T. et al. APOE-\u03b52 and APOE-\u03b54 correlate with increased amyloid accumulation in cerebral vasculature. J. Neuropathol. Exp. Neurol. 72, 708\u2013715 (2013).","journal-title":"J. Neuropathol. Exp. Neurol."},{"key":"2473_CR4","doi-asserted-by":"publisher","first-page":"605","DOI":"10.1038\/s41588-024-01685-y","volume":"56","author":"M Fujita","year":"2024","unstructured":"Fujita, M. et al. Cell subtype-specific effects of genetic variation in the Alzheimer\u2019s disease brain. Nat. Genet. 56, 605\u2013614 (2024).","journal-title":"Nat. Genet."},{"key":"2473_CR5","doi-asserted-by":"publisher","unstructured":"Belloy, M. E., Graff-Radford, J. & Greicius, M. D. A quantitative trait locus for reduced microglial APOE expression associates with reduced cerebral amyloid angiopathy. Preprint at medRxiv https:\/\/doi.org\/10.1101\/2025.03.10.25323519 (2025).","DOI":"10.1101\/2025.03.10.25323519"},{"key":"2473_CR6","doi-asserted-by":"publisher","first-page":"1331","DOI":"10.1038\/s43587-024-00719-8","volume":"4","author":"M Hawrylycz","year":"2024","unstructured":"Hawrylycz, M. et al. SEA-AD is a multimodal cellular atlas and resource for Alzheimer\u2019s disease. Nat. Aging 4, 1331\u20131334 (2024).","journal-title":"Nat. Aging"},{"key":"2473_CR7","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-024-46315-7","volume":"15","author":"A Podle\u015bny-Drabiniok","year":"2024","unstructured":"Podle\u015bny-Drabiniok, A. et al. BHLHE40\/41 regulate microglia and peripheral macrophage responses associated with Alzheimer\u2019s disease and other disorders of lipid-rich tissues. Nat. Commun. 15, 2058 (2024).","journal-title":"Nat. Commun."},{"key":"2473_CR8","doi-asserted-by":"publisher","DOI":"10.1080\/07853890.2024.2445194","volume":"57","author":"H Hu","year":"2025","unstructured":"Hu, H. et al. Deciphering the role of APOE in cerebral amyloid angiopathy: from genetic insights to therapeutic horizons. Ann. Med. 57, 2445194 (2025).","journal-title":"Ann. Med."},{"key":"2473_CR9","volume":"12","author":"RM Walker","year":"2020","unstructured":"Walker, R. M. et al. Epigenome-wide analyses identify DNA methylation signatures of dementia risk. Alzheimers Dement. (Amst.) 12, e12078 (2020).","journal-title":"Alzheimers Dement. (Amst.)"},{"key":"2473_CR10","doi-asserted-by":"publisher","first-page":"459","DOI":"10.1038\/s10038-017-0393-8","volume":"63","author":"Y Shao","year":"2018","unstructured":"Shao, Y. et al. DNA methylation of TOMM40-APOE-APOC2 in Alzheimer\u2019s disease. J. Hum. Genet. 63, 459\u2013471 (2018).","journal-title":"J. Hum. Genet."},{"key":"2473_CR11","doi-asserted-by":"publisher","first-page":"2366","DOI":"10.1038\/s41593-024-01774-5","volume":"27","author":"MI Gabitto","year":"2024","unstructured":"Gabitto, M. I. et al. Integrated multimodal cell atlas of Alzheimer\u2019s disease. Nat. Neurosci. 27, 2366\u20132383 (2024).","journal-title":"Nat. Neurosci."},{"key":"2473_CR12","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":"2473_CR13","doi-asserted-by":"publisher","unstructured":"Poplin, R. et al. Scaling accurate genetic variant discovery to tens of thousands of samples. Preprint at bioRxiv https:\/\/doi.org\/10.1101\/201178 (2018).","DOI":"10.1101\/201178"},{"key":"2473_CR14","doi-asserted-by":"publisher","first-page":"1297","DOI":"10.1101\/gr.107524.110","volume":"20","author":"A McKenna","year":"2010","unstructured":"McKenna, A. et al. The Genome Analysis Toolkit: a MapReduce framework for analyzing next-generation DNA sequencing data. Genome Res. 20, 1297\u20131303 (2010).","journal-title":"Genome Res."},{"key":"2473_CR15","doi-asserted-by":"publisher","first-page":"491","DOI":"10.1038\/ng.806","volume":"43","author":"MA DePristo","year":"2011","unstructured":"DePristo, M. A. et al. A framework for variation discovery and genotyping using next-generation DNA sequencing data. Nat. Genet. 43, 491\u2013498 (2011).","journal-title":"Nat. Genet."},{"key":"2473_CR16","doi-asserted-by":"crossref","first-page":"11.10.11","DOI":"10.1002\/0471250953.bi1110s43","volume":"43","author":"GA Van der Auwera","year":"2013","unstructured":"Van der Auwera, G. A. et al. From FastQ data to high confidence variant calls: the Genome Analysis Toolkit best practices pipeline. Curr. Protoc. Bioinformatics 43, 11.10.11\u201311.10.33 (2013).","journal-title":"Curr. Protoc. Bioinformatics"},{"key":"2473_CR17","unstructured":"Van der Auwera, G. A. & O\u2019Connor, B. D. Genomics in the Cloud: Using Docker, GATK, and WDL in Terra (O\u2019Reilly Media, 2020)."},{"key":"2473_CR18","doi-asserted-by":"publisher","first-page":"1053","DOI":"10.1038\/s41592-018-0229-2","volume":"15","author":"R Lopez","year":"2018","unstructured":"Lopez, R. et al. Deep generative modeling for single-cell transcriptomics. Nat. Methods 15, 1053\u20131058 (2018).","journal-title":"Nat. Methods"},{"key":"2473_CR19","doi-asserted-by":"publisher","DOI":"10.15252\/msb.20209620","volume":"17","author":"C Xu","year":"2021","unstructured":"Xu, C. et al. Probabilistic harmonization and annotation of single-cell transcriptomics data with deep generative models. Mol. Syst. Biol. 17, e9620 (2021).","journal-title":"Mol. Syst. Biol."},{"key":"2473_CR20","doi-asserted-by":"publisher","first-page":"1267","DOI":"10.1038\/s41593-023-01356-x","volume":"26","author":"A Cain","year":"2023","unstructured":"Cain, A. et al. Multicellular communities are perturbed in the aging human brain and Alzheimer\u2019s disease. Nat. Neurosci. 26, 1267\u20131280 (2023).","journal-title":"Nat. Neurosci."},{"key":"2473_CR21","doi-asserted-by":"publisher","first-page":"293","DOI":"10.1038\/s41587-023-01767-y","volume":"42","author":"Y Hao","year":"2024","unstructured":"Hao, Y. et al. Dictionary learning for integrative, multimodal and scalable single-cell analysis. Nat. Biotechnol. 42, 293\u2013304 (2024).","journal-title":"Nat. Biotechnol."},{"key":"2473_CR22","doi-asserted-by":"publisher","first-page":"139","DOI":"10.1093\/bioinformatics\/btp616","volume":"26","author":"MD Robinson","year":"2010","unstructured":"Robinson, M. D., McCarthy, D. J. & Smyth, G. K. edgeR: a Bioconductor package for differential expression analysis of digital gene expression data. Bioinformatics 26, 139\u2013140 (2010).","journal-title":"Bioinformatics"},{"key":"2473_CR23","doi-asserted-by":"publisher","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, e47 (2015).","journal-title":"Nucleic Acids Res."},{"key":"2473_CR24","doi-asserted-by":"publisher","first-page":"882","DOI":"10.1093\/bioinformatics\/bts034","volume":"28","author":"JT Leek","year":"2012","unstructured":"Leek, J. T. et al. The sva package for removing batch effects and other unwanted variation in high-throughput experiments. Bioinformatics 28, 882\u2013883 (2012).","journal-title":"Bioinformatics"},{"key":"2473_CR25","doi-asserted-by":"publisher","first-page":"1353","DOI":"10.1093\/bioinformatics\/bts163","volume":"28","author":"AA Shabalin","year":"2012","unstructured":"Shabalin, A. A. Matrix eQTL: ultra fast eQTL analysis via large matrix operations. Bioinformatics 28, 1353\u20131358 (2012).","journal-title":"Bioinformatics"},{"key":"2473_CR26","doi-asserted-by":"publisher","first-page":"1930","DOI":"10.1212\/WNL.0000000000002175","volume":"85","author":"PA Boyle","year":"2015","unstructured":"Boyle, P. A. et al. Cerebral amyloid angiopathy and cognitive outcomes in community-based older persons. Neurology 85, 1930\u20131936 (2015).","journal-title":"Neurology"}],"container-title":["Nature Genetics"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.nature.com\/articles\/s41588-025-02473-y.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/s41588-025-02473-y","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/s41588-025-02473-y.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,2,12]],"date-time":"2026-02-12T14:38:36Z","timestamp":1770907116000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.nature.com\/articles\/s41588-025-02473-y"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,1,26]]},"references-count":26,"journal-issue":{"issue":"2","published-print":{"date-parts":[[2026,2]]}},"alternative-id":["2473"],"URL":"https:\/\/doi.org\/10.1038\/s41588-025-02473-y","relation":{},"ISSN":["1061-4036","1546-1718"],"issn-type":[{"value":"1061-4036","type":"print"},{"value":"1546-1718","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,1,26]]},"assertion":[{"value":"27 August 2025","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"9 December 2025","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"26 January 2026","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"All authors declare no competing interests.","order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}]}}