{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,13]],"date-time":"2026-07-13T08:11:26Z","timestamp":1783930286132,"version":"3.55.0"},"reference-count":38,"publisher":"Wiley","issue":"7","license":[{"start":{"date-parts":[[2026,1,16]],"date-time":"2026-01-16T00:00:00Z","timestamp":1768521600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2026,1,16]],"date-time":"2026-01-16T00:00:00Z","timestamp":1768521600000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/501100005230","name":"Natural Science Foundation of Chongqing Municipality","doi-asserted-by":"publisher","award":["CSTB2024NSCQ\u2010MSX0945 to YX"],"award-info":[{"award-number":["CSTB2024NSCQ\u2010MSX0945 to YX"]}],"id":[{"id":"10.13039\/501100005230","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Ann Clin Transl Neurol"],"published-print":{"date-parts":[[2026,7]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Backgrounds<\/jats:title>\n                    <jats:p>Alzheimer's disease (AD) is characterized by amyloid\u2010beta plaques, tau tangles, and neuroinflammation. C\u2010X3\u2010C motif chemokine ligand 1 (CX3CL1, also known as fractalkine), a neuroimmune chemokine implicated in AD pathogenesis, shows inconsistent alterations in plasma\/serum across studies. Specifically examining age\u2010dependency and diagnostic utility, we investigated plasma CX3CL1 levels across the cognitive continuum (cognitively normal [CN], amnestic mild cognitive impairment [aMCI], AD) in a Chinese cohort.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>A total of 443 participants, including 130 patients with AD, 72 patients with aMCI, and 99 age\u2010and sex\u2010matched CN controls, as well as a cohort of 142 CN subjects of different ages, were enrolled from Chongqing General Hospital. Plasma CX3CL1 levels were determined using Enzyme\u2010Linked Immunosorbent Assay (ELISA). Apolipoprotein E genotypes (APOE) were performed. The correlations between Plasma CX3CL1 levels and cognition test scores or age were analyzed. The optimal diagnostic sensitivity and specificity were determined using receiver operating characteristic curve analysis.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      Plasma CX3CL1 levels significantly increased with age in CN individuals. No significant sex difference was found. Plasma CX3CL1 levels did not differ significantly between APOE \u03b54 carriers and non\u2010carriers. Stepwise elevation across continuum: CX3CL1 levels showed a significant stepwise increase: CN controls (1.73\u2009\u00b1\u20090.51\u2009ng\/mL)\u2009&lt;\u2009aMCI (2.40\u2009\u00b1\u20091.06\u2009ng\/mL)\u2009&lt;\u2009AD (4.15\u2009\u00b1\u20091.24\u2009ng\/mL) (\n                      <jats:italic>p<\/jats:italic>\n                      \u2009&lt;\u20090.001 between all groups). This pattern persisted in both male and female subgroups, between the AD group and the aMCI group, between the AD group and the CN control group (\n                      <jats:italic>p<\/jats:italic>\n                      \u2009&lt;\u20090.001), between the aMCI group and the CN control group, and between the male and female subgroups (\n                      <jats:italic>p<\/jats:italic>\n                      \u2009&lt;\u20090.05). CX3CL1 levels negatively correlated with Mini\u2010Mental State Examination (MMSE) scores and positively correlated with age.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>Plasma CX3CL1 levels exhibit a significant age\u2010dependent increase in cognitively normal individuals, peak in midlife (40\u201349\u2009years), and demonstrate a stepwise elevation across the AD continuum (CN\u2009\u2192\u2009aMCI \u2192 AD). Strong inverse correlations with cognitive scores in disease groups and high diagnostic accuracy for AD, particularly against CN, support its role as a biomarker reflecting both physiological aging and AD\u2010related pathological decline. Its regulation appears independent of APOE \u03b54 status. The midlife peak suggests potential relevance for preclinical processes, warranting further investigation of CX3CL1 as a biomarker and therapeutic target.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/acn3.70320","type":"journal-article","created":{"date-parts":[[2026,1,17]],"date-time":"2026-01-17T04:05:11Z","timestamp":1768622711000},"page":"1335-1345","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["CX3CL1 in Early Detection of Alzheimer's Disease: Plasma Dynamics Across Age and Disease Stages"],"prefix":"10.1002","volume":"13","author":[{"ORCID":"https:\/\/orcid.org\/0009-0009-6725-0737","authenticated-orcid":false,"given":"Ling","family":"Wang","sequence":"first","affiliation":[{"name":"Chongqing Medical University  Chongqing China"},{"name":"Department of Geriatrics, Chongqing General Hospital Chongqing University  Chongqing 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