{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,1,10]],"date-time":"2026-01-10T08:07:19Z","timestamp":1768032439567,"version":"3.49.0"},"reference-count":48,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2025,1,3]],"date-time":"2025-01-03T00:00:00Z","timestamp":1735862400000},"content-version":"vor","delay-in-days":2,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100005089","name":"Natural Science Foundation of Beijing Municipality","doi-asserted-by":"publisher","award":["L232136"],"award-info":[{"award-number":["L232136"]}],"id":[{"id":"10.13039\/501100005089","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["82271452"],"award-info":[{"award-number":["82271452"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["CNS Neurosci Ther"],"published-print":{"date-parts":[[2025,1]]},"abstract":"<jats:title>ABSTRACT<\/jats:title><jats:sec><jats:title>Aims<\/jats:title><jats:p>To analyze the effect of <jats:italic>APOE \u03b5<\/jats:italic>4 on fluid biomarkers and the correlations between blood molecules and CSF biomarkers in AD patients.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>This study enrolled 575\u2009AD patients, 131 patients with non\u2010AD dementia, and 112 cognitively normal (CN) participants, and AD patients were divided into <jats:italic>APOE \u03b5<\/jats:italic>4 carriers and non\u2010carriers. Cerebrospinal fluid (CSF) biomarkers and blood\u2010derived biomolecules were compared between AD and CN groups, between non\u2010AD dementia and CN groups, as well as within <jats:italic>APOE \u03b5<\/jats:italic>4 subgroups of AD patients. Utilizing Spearman's correlation analysis and quantile regression analysis, the relationships between blood\u2010derived biomolecules and CSF biomarkers were analyzed in <jats:italic>APOE \u03b5<\/jats:italic>4 carriers and non\u2010carriers.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>The levels of CSF biomarkers and blood molecules exhibited significant differences between the AD and CN groups, including A\u03b242, t\u2010tau, p\u2010tau 181, high\u2010density lipoprotein, low\u2010density lipoprotein (LDL), and uric acid. In AD patients, <jats:italic>APOE \u03b5<\/jats:italic>4 carriers had increased levels of CSF t\u2010tau, p\u2010tau 181, and plasma LDL. In the correlation and regression analyses, the negative relationships between plasma TG and t\u2010tau, between plasma TG and p\u2010tau 181 levels, as well as the positive relationship between serum IgA and CSF A\u03b242, were observed significantly in <jats:italic>APOE \u03b5<\/jats:italic>4+ AD groups, but not in <jats:italic>APOE \u03b5<\/jats:italic>4\u2212 AD group.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p><jats:italic>APOE \u03b5<\/jats:italic>4 is associated with accelerated progression of AD pathology. The blood\u2010derived biomolecules correlated with CSF biomarkers in <jats:italic>APOE \u03b5<\/jats:italic>4 carriers are related to neuroinflammation and lipid metabolism, which may indicate the role of <jats:italic>APOE \u03b5<\/jats:italic>4 in AD pathophysiology and offer insights for diagnostic and therapeutic strategies for AD.<\/jats:p><\/jats:sec><jats:sec><jats:title>Trial Registration<\/jats:title><jats:p><jats:ext-link xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" xlink:href=\"http:\/\/clinicaltrials.gov\">ClinicalTrials.gov<\/jats:ext-link> identifier: NCT03653156<\/jats:p><\/jats:sec>","DOI":"10.1111\/cns.70202","type":"journal-article","created":{"date-parts":[[2025,1,3]],"date-time":"2025-01-03T10:36:08Z","timestamp":1735900568000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["The Effect of <i>APOE \u03b5<\/i>4 on Alzheimer's Disease Fluid Biomarkers: A Cross\u2010Sectional Study Based on the <scp>COAST<\/scp>"],"prefix":"10.1111","volume":"31","author":[{"given":"Bote","family":"Zhao","sequence":"first","affiliation":[{"name":"Innovation Center for Neurological Disorders and Department of Neurology, Xuanwu Hospital Capital Medical University  Beijing China"},{"name":"National Center for Neurological Disorders and National Clinical Research Center for Geriatric Diseases  Beijing China"},{"name":"Center of Alzheimer's Disease, Beijing Institute of Brain Disorders Collaborative Innovation Center for Brain Disorders  Beijing China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Peixi","family":"Zang","sequence":"additional","affiliation":[{"name":"Innovation Center for Neurological Disorders and Department of Neurology, Xuanwu Hospital Capital Medical University  Beijing China"},{"name":"Department of Neurology Gansu Provincial Hospital  Lanzhou City Gansu Province China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Meina","family":"Quan","sequence":"additional","affiliation":[{"name":"Innovation Center for Neurological Disorders and Department of Neurology, Xuanwu Hospital Capital Medical University  Beijing China"},{"name":"National Center for Neurological Disorders and National Clinical Research Center for Geriatric Diseases  Beijing China"},{"name":"Center of Alzheimer's Disease, Beijing Institute of Brain Disorders Collaborative Innovation Center for Brain Disorders  Beijing China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Qianqian","family":"Wang","sequence":"additional","affiliation":[{"name":"Innovation Center for Neurological Disorders and Department of Neurology, Xuanwu Hospital Capital Medical University  Beijing China"},{"name":"National Center for Neurological Disorders and National Clinical Research Center for Geriatric Diseases  Beijing China"},{"name":"Center of Alzheimer's Disease, Beijing Institute of Brain Disorders Collaborative Innovation Center for Brain Disorders  Beijing China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Dongmei","family":"Guo","sequence":"additional","affiliation":[{"name":"Innovation Center for Neurological Disorders and Department of Neurology, Xuanwu Hospital Capital Medical University  Beijing China"},{"name":"National Center for Neurological Disorders and National Clinical Research Center for Geriatric Diseases  Beijing China"},{"name":"Center of Alzheimer's Disease, Beijing Institute of Brain Disorders Collaborative Innovation Center for Brain Disorders  Beijing China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jianping","family":"Jia","sequence":"additional","affiliation":[{"name":"Innovation Center for Neurological Disorders and Department of Neurology, Xuanwu Hospital Capital Medical University  Beijing China"},{"name":"National Center for Neurological Disorders and National Clinical Research Center for Geriatric Diseases  Beijing China"},{"name":"Center of Alzheimer's Disease, Beijing Institute of Brain Disorders Collaborative Innovation Center for Brain Disorders  Beijing China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2044-6387","authenticated-orcid":false,"given":"Wei","family":"Wang","sequence":"additional","affiliation":[{"name":"Innovation Center for Neurological Disorders and Department of Neurology, Xuanwu Hospital Capital Medical University  Beijing China"},{"name":"National Center for Neurological Disorders and National Clinical Research Center for Geriatric Diseases  Beijing China"},{"name":"Center of Alzheimer's Disease, Beijing Institute of Brain Disorders Collaborative Innovation Center for Brain Disorders  Beijing China"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2025,1,3]]},"reference":[{"key":"e_1_2_10_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(20)32205-4"},{"key":"e_1_2_10_3_1","doi-asserted-by":"publisher","DOI":"10.1212\/WNL.0000000000004336"},{"key":"e_1_2_10_4_1","doi-asserted-by":"publisher","DOI":"10.3233\/JAD-181282"},{"key":"e_1_2_10_5_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41582-019-0228-7"},{"key":"e_1_2_10_6_1","doi-asserted-by":"publisher","DOI":"10.1212\/WNL.43.8.1467"},{"key":"e_1_2_10_7_1","doi-asserted-by":"publisher","DOI":"10.1186\/s13195-023-01192-y"},{"key":"e_1_2_10_8_1","doi-asserted-by":"publisher","DOI":"10.3233\/JAD-215067"},{"key":"e_1_2_10_9_1","doi-asserted-by":"publisher","DOI":"10.1186\/s13195-023-01262-1"},{"key":"e_1_2_10_10_1","doi-asserted-by":"publisher","DOI":"10.1001\/jamanetworkopen.2020.9250"},{"key":"e_1_2_10_11_1","doi-asserted-by":"publisher","DOI":"10.1186\/s13195-022-01062-z"},{"key":"e_1_2_10_12_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jalz.2018.07.223"},{"key":"e_1_2_10_13_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0172268"},{"key":"e_1_2_10_14_1","doi-asserted-by":"publisher","DOI":"10.1136\/annrheumdis-2014-206917"},{"key":"e_1_2_10_15_1","doi-asserted-by":"publisher","DOI":"10.1016\/S1474-4422(21)00361-6"},{"key":"e_1_2_10_16_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jalz.2011.03.005"},{"key":"e_1_2_10_17_1","doi-asserted-by":"publisher","DOI":"10.1016\/0022-3956(75)90026-6"},{"key":"e_1_2_10_18_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1532-5415.2005.53221.x"},{"key":"e_1_2_10_19_1","doi-asserted-by":"publisher","DOI":"10.1093\/gerona\/gls006"},{"key":"e_1_2_10_20_1","doi-asserted-by":"publisher","DOI":"10.1001\/archneur.65.7.963"},{"key":"e_1_2_10_21_1","doi-asserted-by":"publisher","DOI":"10.1023\/B:AIRE.0000045502.10941.a9"},{"key":"e_1_2_10_22_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neurobiolaging.2015.09.011"},{"key":"e_1_2_10_23_1","doi-asserted-by":"publisher","DOI":"10.1001\/jamaneurol.2021.1893"},{"key":"e_1_2_10_24_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.294.5545.1354"},{"key":"e_1_2_10_25_1","doi-asserted-by":"publisher","DOI":"10.1186\/s12929-019-0524-y"},{"key":"e_1_2_10_26_1","doi-asserted-by":"publisher","DOI":"10.1001\/jamanetworkopen.2023.13734"},{"key":"e_1_2_10_27_1","doi-asserted-by":"publisher","DOI":"10.1001\/jamaneurol.2019.0648"},{"key":"e_1_2_10_28_1","doi-asserted-by":"publisher","DOI":"10.1186\/s13195-020-00690-7"},{"key":"e_1_2_10_29_1","doi-asserted-by":"publisher","DOI":"10.1212\/WNL.0000000000207876"},{"key":"e_1_2_10_30_1","doi-asserted-by":"publisher","DOI":"10.1001\/archneur.61.5.705"},{"key":"e_1_2_10_31_1","doi-asserted-by":"publisher","DOI":"10.1093\/cvr\/cvab164"},{"key":"e_1_2_10_32_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neulet.2013.06.063"},{"key":"e_1_2_10_33_1","doi-asserted-by":"publisher","DOI":"10.1002\/ana.20469"},{"key":"e_1_2_10_34_1","doi-asserted-by":"publisher","DOI":"10.1111\/jnc.15681"},{"key":"e_1_2_10_35_1","doi-asserted-by":"publisher","DOI":"10.1212\/WNL.0000000000207923"},{"key":"e_1_2_10_36_1","doi-asserted-by":"publisher","DOI":"10.1126\/scitranslmed.aaz4564"},{"key":"e_1_2_10_37_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41586-024-07185-7"},{"key":"e_1_2_10_38_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0197-4580(00)00124-X"},{"key":"e_1_2_10_39_1","doi-asserted-by":"publisher","DOI":"10.1002\/alz.12799"},{"key":"e_1_2_10_40_1","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.0829-08.2008"},{"key":"e_1_2_10_41_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.162350199"},{"key":"e_1_2_10_42_1","doi-asserted-by":"publisher","DOI":"10.1186\/s40478-016-0339-y"},{"key":"e_1_2_10_43_1","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2013.00185"},{"key":"e_1_2_10_44_1","doi-asserted-by":"publisher","DOI":"10.3233\/JAD-191111"},{"key":"e_1_2_10_45_1","doi-asserted-by":"publisher","DOI":"10.1007\/s12035-015-9271-6"},{"key":"e_1_2_10_46_1","doi-asserted-by":"publisher","DOI":"10.3389\/fnagi.2022.742408"},{"key":"e_1_2_10_47_1","doi-asserted-by":"publisher","DOI":"10.1212\/WNL.0000000000200953"},{"key":"e_1_2_10_48_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41598-020-71832-y"},{"key":"e_1_2_10_49_1","doi-asserted-by":"publisher","DOI":"10.1007\/s11011-022-01114-1"}],"container-title":["CNS Neuroscience &amp; Therapeutics"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/cns.70202","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,4,26]],"date-time":"2025-04-26T05:59:19Z","timestamp":1745647159000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1111\/cns.70202"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,1]]},"references-count":48,"journal-issue":{"issue":"1","published-print":{"date-parts":[[2025,1]]}},"alternative-id":["10.1111\/cns.70202"],"URL":"https:\/\/doi.org\/10.1111\/cns.70202","archive":["Portico"],"relation":{},"ISSN":["1755-5930","1755-5949"],"issn-type":[{"value":"1755-5930","type":"print"},{"value":"1755-5949","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,1]]},"assertion":[{"value":"2024-09-15","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2024-12-18","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2025-01-03","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"e70202"}}