{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,28]],"date-time":"2026-04-28T17:28:55Z","timestamp":1777397335280,"version":"3.51.4"},"reference-count":63,"publisher":"SAGE Publications","issue":"3","license":[{"start":{"date-parts":[[2025,4,22]],"date-time":"2025-04-22T00:00:00Z","timestamp":1745280000000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.sagepub.com\/page\/policies\/text-and-data-mining-license"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["81701675"],"award-info":[{"award-number":["81701675"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["journals.sagepub.com"],"crossmark-restriction":true},"short-container-title":["Journal of Alzheimer\u2019s Disease"],"published-print":{"date-parts":[[2025,6]]},"abstract":"<jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>\n                      The apolipoprotein E \u03b54 allele (\n                      <jats:italic>APOE<\/jats:italic>\n                      \u03b54) and inflammation are associated with Alzheimer's disease (AD) pathology. Mild cognitive impairment (MCI) is considered the preclinical and early stage of AD. However, the comprehensive effects of\n                      <jats:italic>APOE<\/jats:italic>\n                      \u03b54 and inflammatory mediators on MCI patients with specific\n                      <jats:italic>APOE<\/jats:italic>\n                      \u03b54 genotypes remain poorly understood.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Objective<\/jats:title>\n                    <jats:p>\n                      Our study aimed to explore how different numbers of the\n                      <jats:italic>APOE<\/jats:italic>\n                      \u03b54 alleles affect plasma C-reactive protein (CRP) and interleukin-3 (IL-3) levels and their associations with brain structure.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      A total of 339 MCI patients from the Alzheimer's Disease Neuroimaging Initiative study were enrolled. We compared their plasma concentrations of CRP and IL-3, cognitive performance, and cerebrospinal fluid (CSF) AD biomarkers levels across different\n                      <jats:italic>APOE<\/jats:italic>\n                      \u03b54 genotypes. Structural magnetic resonance imaging was utilized to measure gray matter volume outcomes. Pearson correlation analysis was used to explore the associations between the above indicators.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      Plasma CRP levels increased in the\n                      <jats:italic>APOE<\/jats:italic>\n                      \u03b54 carriers, but IL-3 expression notably decreased, and the homozygous state is the most significant. A negative correlation between CRP and several cognitive abilities was observed only in\n                      <jats:italic>APOE<\/jats:italic>\n                      \u03b54 homozygotes. Additionally, a positive correlation between IL-3, cognitive scores, and CSF biomarker levels was confirmed only in\n                      <jats:italic>APOE<\/jats:italic>\n                      \u03b54 homozygotes. Imaging data demonstrated that the gray matter volume of the right middle frontal gyrus was associated with CRP only in\n                      <jats:italic>APOE<\/jats:italic>\n                      \u03b54 non-carriers.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>\n                      Our study demonstrated that peripheral inflammatory mediators\u2019 effect on cognitive function and brain structure in MCI patients differs based on their\n                      <jats:italic>APOE<\/jats:italic>\n                      \u03b54 allele carrier status.\n                    <\/jats:p>\n                  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