{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,7]],"date-time":"2026-10-07T01:29:24Z","timestamp":1791336564001,"version":"4.3.1"},"reference-count":52,"publisher":"American Medical Association (AMA)","issue":"5","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["JAMA Netw Open"],"abstract":"\n Importance<\/jats:title>\n \n Scarce population-based data exist on whether\n APOE4<\/jats:italic>\n modifies associations of blood-based neurodegenerative biomarkers with cognitive decline, particularly in a diverse, biracial population of community-dwelling older adults without dementia.\n <\/jats:p>\n <\/jats:sec>\n \n Objective<\/jats:title>\n \n To assess whether\n APOE4<\/jats:italic>\n carrier status is associated with an accelerated rate of cognitive decline in older adults without dementia and with elevated neurodegenerative burden.\n <\/jats:p>\n <\/jats:sec>\n \n Design, Setting, and Participants<\/jats:title>\n \n This 20-year prospective cohort study started in 1993 and was conducted through 2012 on the South Side of Chicago among community-dwelling older adults without dementia from the longitudinal biracial Chicago Health and Aging Project. The interaction of\n APOE4<\/jats:italic>\n carrier status with prospective associations of serum neurodegenerative biomarkers with global cognitive decline was examined using a mixed-effects regression model, adjusting for demographics and chronic health conditions. Statistical analyses were conducted from June 2024 to January 2025.\n <\/jats:p>\n <\/jats:sec>\n \n Exposure<\/jats:title>\n \n APOE4<\/jats:italic>\n carrier status and serum biomarker levels for total tau (t-tau), neurofilament light (NfL) chain, and glial fibrillary acidic protein (GFAP) measured with a Quanterix Neuroplex kit at baseline.\n <\/jats:p>\n <\/jats:sec>\n \n Main Outcomes and Measures<\/jats:title>\n Cognitive decline calculated from composite global cognition scores across study waves.<\/jats:p>\n <\/jats:sec>\n \n Results<\/jats:title>\n \n Among 1038 community-dwelling older adults (mean [SD] age, 77.1 [5.9] years; 615 Black [59.2%] and 423 White [40.8%]; 651 female [62.7%]), there was a mean (SD) of 12.8 (3.4) years of education and 343 individuals (33.0%) were\n APOE4<\/jats:italic>\n carriers. Higher levels of blood-based neurodegenerative biomarkers (ie, t-tau, NfL, and GFAP) were associated with a faster rate of cognitive decline among\n APOE4<\/jats:italic>\n carriers than noncarriers. Specifically, compared with noncarriers,\n APOE4<\/jats:italic>\n carriers had annual rates of cognitive decline per 1\u2013log\n 10<\/jats:sub>\n unit higher levels in t-tau and GFAP that were accelerated by a \u03b2 (SD) of \u22120.03 (0.02) (\n P<\/jats:italic>\n \u2009=\u2009.046) and \u22120.07 (0.03) (\n P<\/jats:italic>\n \u2009=\u2009.02), respectively. Similarly, compared with noncarriers and participants in the lower NfL tertile,\n APOE4<\/jats:italic>\n carriers with middle and upper tertiles of NfL levels experienced accelerated cognitive decline, with a \u03b2 (SD) of \u22120.04 (0.02) (\n P<\/jats:italic>\n \u2009=\u2009.006) and \u22120.03 (0.02) (\n P<\/jats:italic>\n \u2009=\u2009.07), respectively, although the difference was not significant for upper tertiles.\n <\/jats:p>\n <\/jats:sec>\n \n Conclusions and Relevance<\/jats:title>\n \n This study found that higher levels of neurodegeneration (t-tau), axonal injury (NfL), and reactive astrocytes and neuroinflammation (GFAP) biomarkers were associated with accelerated cognitive decline in genetically susceptible\n APOE4<\/jats:italic>\n carriers. These findings highlight the association of\n APOE4<\/jats:italic>\n with exacerbation of neurodegenerative processes, with not only significant implications for understanding and tracking the progression of neurodegenerative diseases, but also a call for inclusivity of\n APOE4<\/jats:italic>\n status in scientific investigations and clinical trials.\n <\/jats:p>\n <\/jats:sec>","DOI":"10.1001\/jamanetworkopen.2025.8903","type":"journal-article","created":{"date-parts":[[2025,5,7]],"date-time":"2025-05-07T11:48:29Z","timestamp":1746618509000},"page":"e258903","source":"Crossref","is-referenced-by-count":28,"title":["APOE4<\/i>\n , Blood Neurodegenerative Biomarkers, and Cognitive Decline in Community-Dwelling Older Adults"],"prefix":"10.1001","volume":"8","author":[{"given":"Ted K. 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