{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,5]],"date-time":"2026-08-05T10:47:40Z","timestamp":1785926860867,"version":"3.56.0"},"reference-count":48,"publisher":"Wiley","issue":"3","license":[{"start":{"date-parts":[[2019,7,22]],"date-time":"2019-07-22T00:00:00Z","timestamp":1563753600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/100000049","name":"National Institute on Aging","doi-asserted-by":"publisher","award":["43885, 42856, 25688 and K01AG042498"],"award-info":[{"award-number":["43885, 42856, 25688 and K01AG042498"]}],"id":[{"id":"10.13039\/100000049","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Annals of Neurology"],"published-print":{"date-parts":[[2019,9]]},"abstract":"<jats:sec><jats:title>Objective<\/jats:title><jats:p>Compared to older Caucasians, older African Americans have higher risks of developing Alzheimer disease (AD) and lower cerebrospinal fluid (CSF) tau biomarker levels. It is not known whether tau\u2010related differences begin earlier in life or whether race modifies other AD\u2010related biomarkers such as inflammatory proteins.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>We performed multiplex cytokine analysis in a healthy middle\u2010aged cohort with family history of AD (n = 68) and an older cohort (n = 125) with normal cognition (NC), mild cognitive impairment, or AD dementia. After determining baseline interleukin (IL)\u20109 level and AD\u2010associated IL\u20109 change to differ according to race, we performed immunohistochemical analysis for proteins mechanistically linked to IL\u20109 in brains of African Americans and Caucasians (n = 38), and analyzed postmortem IL\u20109\u2013related gene expression profiles in the publicly available Mount Sinai cohort (26 African Americans and 180 Caucasians).<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Compared to Caucasians with NC, African Americans with NC had lower CSF tau, p\u2010Tau<jats:sub>181<\/jats:sub>, and IL\u20109 levels in both living cohorts. Conversely, AD was only correlated with increased CSF IL\u20109 levels in African Americans but not Caucasians. Immunohistochemical analysis revealed perivascular, neuronal, and glial cells immunoreactive to IL\u20109, and quantitative analysis in independent US cohorts showed AD to correlate with molecular changes (upstream differentiation marker and downstream effector cell marker) of IL\u20109 upregulation only in African Americans but not Caucasians.<\/jats:p><\/jats:sec><jats:sec><jats:title>Interpretation<\/jats:title><jats:p>Baseline and AD\u2010associated IL\u20109 differences between African Americans and Caucasians point to distinct molecular phenotypes for AD according to ancestry. Genetic and nongenetic factors need to be considered in future AD research involving unique populations. 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