{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,17]],"date-time":"2026-09-17T16:48:22Z","timestamp":1789663702026,"version":"4.0.1"},"reference-count":44,"publisher":"Wiley","issue":"6","license":[{"start":{"date-parts":[[2025,3,9]],"date-time":"2025-03-09T00:00:00Z","timestamp":1741478400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2025,3,9]],"date-time":"2025-03-09T00:00:00Z","timestamp":1741478400000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/501100012166","name":"National Key Research and Development Program of China","doi-asserted-by":"publisher","award":["2023YFC3605400"],"award-info":[{"award-number":["2023YFC3605400"]}],"id":[{"id":"10.13039\/501100012166","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Aging Cell"],"published-print":{"date-parts":[[2025,6]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>\n                    Revealing the temporal evolution of cerebrospinal fluid (CSF) biomarkers during aging is critical to understanding disease pathogenesis and developing early diagnoses and interventions for Alzheimer's disease (AD). CSF was obtained from 549 cognitively normal subjects between 18 and 93\u2009years of age. 12\u2009AD\u2010related biomarkers were evaluated, including amyloid \u03b2 (A\u03b242, A\u03b240, A\u03b242\/A\u03b240 ratio), hyperphosphorylated tau (P\u2010tau), neuronal injury\/degeneration (T\u2010tau, NFL, NSE, H\u2010FABP, VILIP\u20101), neuroinflammation biomarkers (YKL\u201040, TREM2), and \u03b1\u2010synuclein (\u03b1\u2010synuclein). Associations between these biomarkers and age as well as apolipoprotein E (\n                    <jats:italic>APOE<\/jats:italic>\n                    ) \u03b54 status were evaluated, and the associations among biomarkers were assessed. CSF A\u03b242, P\u2010tau, and T\u2010tau levels exhibited nonlinear associations with age, among which A\u03b242 was significantly modulated by\n                    <jats:italic>APOE<\/jats:italic>\n                    \u03b54 status. Specifically, an accelerated decline in A\u03b242 levels occurred at 45.69\u2009years of age in the\n                    <jats:italic>APOE<\/jats:italic>\n                    \u03b54+ group, which was almost 23\u2009years earlier than that in the\n                    <jats:italic>APOE<\/jats:italic>\n                    \u03b54\u2212 group (68.02\u2009years). The age\u2010related change pattern of CSF P\u2010tau is similar to that of T\u2010tau, with both increasing slightly with age but showing an accelerated change at \u224860\u2009years of age in the\n                    <jats:italic>APOE<\/jats:italic>\n                    \u03b54+ group. All the other biomarkers except for \u03b1\u2010synuclein were linearly associated with age, and\n                    <jats:italic>APOE<\/jats:italic>\n                    \u03b54 status had no effect on these associations. Most biomarkers were positively correlated with each other except for A\u03b242\/A\u03b240 ratio. The evolution of AD\u2010related biomarkers in CSF varies throughout the adult lifespan, with the APOE \u03b54 allele modifying the temporal changes in CSF A\u03b242 levels, as well as potentially influencing P\u2010tau and T\u2010tau levels.\n                  <\/jats:p>","DOI":"10.1111\/acel.70036","type":"journal-article","created":{"date-parts":[[2025,3,10]],"date-time":"2025-03-10T12:51:45Z","timestamp":1741611105000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Temporal Changes in Alzheimer's Disease\u2010Related Biomarkers in the\n                    <scp>CSF<\/scp>\n                    of Cognitively Normal Subjects at Different Ages: The Chongqing Ageing and Dementia Study"],"prefix":"10.1111","volume":"24","author":[{"given":"Wei\u2010Wei","family":"Li","sequence":"first","affiliation":[{"name":"Department of Neurology and Centre for Clinical Neuroscience, Daping Hospital Third Military Medical University  Chongqing China"},{"name":"Department of Neurology The General Hospital of Western Theater Command  Chengdu China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dong\u2010Yu","family":"Fan","sequence":"additional","affiliation":[{"name":"Department of Neurology and Centre for Clinical Neuroscience, Daping Hospital Third Military Medical University  Chongqing China"},{"name":"Department of Plateau Diseases, Shigatse Branch, Xinqiao Hospital Third Military Medical University  Shigatse China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qi","family":"Sun","sequence":"additional","affiliation":[{"name":"Department of Anesthesiology, Daping Hospital Third Military Medical University  Chongqing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lei\u2010Kai","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Neurosurgery The General Hospital of Western Theater Command  Chengdu China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bing\u2010Qiang","family":"Huang","sequence":"additional","affiliation":[{"name":"Department of Anesthesiology, Daping Hospital Third Military Medical University  Chongqing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhong\u2010Yuan","family":"Yu","sequence":"additional","affiliation":[{"name":"Department of Neurology and Centre for Clinical Neuroscience, Daping Hospital Third Military Medical University  Chongqing China"},{"name":"Chongqing Key Laboratory of Aging and Brain Diseases  Chongqing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ding\u2010Yuan","family":"Tian","sequence":"additional","affiliation":[{"name":"Department of Neurology and Centre for Clinical Neuroscience, Daping Hospital Third Military Medical University  Chongqing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ying\u2010Ying","family":"Shen","sequence":"additional","affiliation":[{"name":"Department of Neurology and Centre for Clinical Neuroscience, Daping Hospital Third Military Medical University  Chongqing China"},{"name":"Chongqing Key Laboratory of Aging and Brain Diseases  Chongqing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cheng\u2010Rong","family":"Tan","sequence":"additional","affiliation":[{"name":"Department of Neurology and Centre for Clinical Neuroscience, Daping Hospital Third Military Medical University  Chongqing China"},{"name":"Chongqing Key Laboratory of Aging and Brain Diseases  Chongqing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gui\u2010Hua","family":"Zeng","sequence":"additional","affiliation":[{"name":"Department of Neurology and Centre for Clinical Neuroscience, Daping Hospital Third Military Medical University  Chongqing China"},{"name":"Chongqing Key Laboratory of Aging and Brain Diseases  Chongqing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fan","family":"Zeng","sequence":"additional","affiliation":[{"name":"Department of Neurology and Centre for Clinical Neuroscience, Daping Hospital Third Military Medical University  Chongqing China"},{"name":"Chongqing Key Laboratory of Aging and Brain Diseases  Chongqing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jin","family":"Fan","sequence":"additional","affiliation":[{"name":"Department of Neurology The General Hospital of Western Theater Command  Chengdu China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhen","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Anesthesiology, Daping Hospital Third Military Medical University  Chongqing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yan\u2010Jiang","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Neurology and Centre for Clinical Neuroscience, Daping Hospital Third Military Medical University  Chongqing China"},{"name":"Chongqing Key Laboratory of Aging and Brain Diseases  Chongqing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jun","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Neurology and Centre for Clinical Neuroscience, Daping Hospital Third Military Medical University  Chongqing China"},{"name":"Chongqing Key Laboratory of Aging and Brain Diseases  Chongqing China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2025,3,9]]},"reference":[{"key":"e_1_2_10_2_1","doi-asserted-by":"publisher","DOI":"10.1212\/WNL.0000000000001859"},{"key":"e_1_2_10_3_1","doi-asserted-by":"publisher","DOI":"10.1002\/alz.14039"},{"key":"e_1_2_10_4_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41588\u2010022\u201001024\u2010z"},{"key":"e_1_2_10_5_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0140\u20106736(06)69113\u20107"},{"key":"e_1_2_10_6_1","doi-asserted-by":"publisher","DOI":"10.1373\/clinchem.2004.033688"},{"key":"e_1_2_10_7_1","doi-asserted-by":"publisher","DOI":"10.1186\/s13195\u2010017\u20100276\u20104"},{"key":"e_1_2_10_8_1","doi-asserted-by":"publisher","DOI":"10.3758\/s13428\u2010023\u201002117\u20101"},{"key":"e_1_2_10_9_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.nbd.2022.105630"},{"key":"e_1_2_10_10_1","doi-asserted-by":"publisher","DOI":"10.1001\/jamaneurol.2014.3314"},{"key":"e_1_2_10_11_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41591\u2010024\u201002931\u2010w"},{"key":"e_1_2_10_12_1","doi-asserted-by":"publisher","DOI":"10.1016\/s1474\u20104422(23)00447\u20107"},{"key":"e_1_2_10_13_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41591\u2010019\u20100675\u20100"},{"key":"e_1_2_10_14_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.arr.2023.102046"},{"key":"e_1_2_10_15_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41380\u2010021\u201001249\u20100"},{"key":"e_1_2_10_16_1","unstructured":"Harrell F. E.2012.\u201cRegression Modeling Strategies. R Package Version 6.2\u20100.\u201d"},{"key":"e_1_2_10_17_1","doi-asserted-by":"publisher","DOI":"10.1038\/tp.2016.252"},{"key":"e_1_2_10_18_1","doi-asserted-by":"publisher","DOI":"10.1001\/jamaneurol.2020.3780"},{"key":"e_1_2_10_19_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jalz.2018.02.018"},{"key":"e_1_2_10_20_1","doi-asserted-by":"publisher","DOI":"10.1001\/jama.2015.4668"},{"key":"e_1_2_10_21_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa2310168"},{"key":"e_1_2_10_22_1","doi-asserted-by":"publisher","DOI":"10.1093\/lifemedi\/lnad017"},{"key":"e_1_2_10_23_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41582\u2010024\u201000955\u2010x"},{"key":"e_1_2_10_24_1","doi-asserted-by":"publisher","DOI":"10.1186\/s13195\u2010017\u20100313\u20103"},{"key":"e_1_2_10_25_1","doi-asserted-by":"publisher","DOI":"10.1186\/s13195\u2010017\u20100271\u20109"},{"key":"e_1_2_10_26_1","doi-asserted-by":"publisher","DOI":"10.1093\/brain\/awac238"},{"key":"e_1_2_10_27_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.arr.2021.101544"},{"key":"e_1_2_10_28_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jalz.2011.05.2243"},{"key":"e_1_2_10_29_1","doi-asserted-by":"publisher","DOI":"10.3390\/medicina58010060"},{"key":"e_1_2_10_30_1","doi-asserted-by":"publisher","DOI":"10.1007\/s40520\u2010019\u201001458\u20102"},{"key":"e_1_2_10_31_1","doi-asserted-by":"publisher","DOI":"10.1097\/wco.0000000000000912"},{"key":"e_1_2_10_32_1","doi-asserted-by":"publisher","DOI":"10.1002\/ana.21843"},{"key":"e_1_2_10_33_1","doi-asserted-by":"publisher","DOI":"10.1016\/s2468\u20102667(24)00120\u20108"},{"key":"e_1_2_10_34_1","doi-asserted-by":"publisher","DOI":"10.1016\/s1474\u20104422(16)00070\u20103"},{"key":"e_1_2_10_35_1","doi-asserted-by":"publisher","DOI":"10.1016\/s1474\u20104422(22)00168\u20105"},{"key":"e_1_2_10_36_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41467\u2010019\u201014279\u20108"},{"key":"e_1_2_10_37_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41582\u2010023\u201000789\u2010z"},{"key":"e_1_2_10_38_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neurobiolaging.2015.04.001"},{"key":"e_1_2_10_39_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pmed.1003289"},{"key":"e_1_2_10_40_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neulet.2014.04.007"},{"key":"e_1_2_10_41_1","doi-asserted-by":"publisher","DOI":"10.15252\/emmm.201606210"},{"key":"e_1_2_10_42_1","doi-asserted-by":"publisher","DOI":"10.1002\/ana.22448"},{"key":"e_1_2_10_43_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00401\u2010013\u20101148\u2010z"},{"key":"e_1_2_10_44_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuron.2017.02.042"},{"key":"e_1_2_10_45_1","doi-asserted-by":"publisher","DOI":"10.1001\/jamaneurol.2024.2713"}],"container-title":["Aging Cell"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/acel.70036","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1111\/acel.70036","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/acel.70036","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,6,10]],"date-time":"2026-06-10T23:09:38Z","timestamp":1781132978000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1111\/acel.70036"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,3,9]]},"references-count":44,"journal-issue":{"issue":"6","published-print":{"date-parts":[[2025,6]]}},"alternative-id":["10.1111\/acel.70036"],"URL":"https:\/\/doi.org\/10.1111\/acel.70036","archive":["Portico"],"relation":{},"ISSN":["1474-9718","1474-9726"],"issn-type":[{"value":"1474-9718","type":"print"},{"value":"1474-9726","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,3,9]]},"assertion":[{"value":"2024-10-16","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2025-02-20","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2025-03-09","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"e70036"}}