{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"institution":[{"name":"medRxiv"}],"indexed":{"date-parts":[[2026,5,19]],"date-time":"2026-05-19T00:11:06Z","timestamp":1779149466652,"version":"3.51.4"},"posted":{"date-parts":[[2026,5,15]]},"group-title":"Neurology","reference-count":77,"publisher":"openRxiv","license":[{"start":{"date-parts":[[2026,5,15]],"date-time":"2026-05-15T00:00:00Z","timestamp":1778803200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"accepted":{"date-parts":[[2026,5,15]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                <jats:sec>\n                  <jats:title>INTRODUCTION<\/jats:title>\n                  <jats:p>Neuroinflammation and immune dysregulation are increasingly recognized as early drivers of Alzheimer\u2019s disease (AD) and AD-related dementias (AD\/ADRD), often emerging decades before the onset of clinical symptoms. Despite this, there remains a critical need for non-invasive biomarkers that can capture these early processes, particularly in African Americans, a population at elevated risk for AD\/ADRD yet underrepresented in neuroimaging research. In this study, we investigated the relationship between systemic plasma inflammatory markers and brain microstructural integrity in cognitively unimpaired older African Americans.<\/jats:p>\n                <\/jats:sec>\n                <jats:sec>\n                  <jats:title>METHODS<\/jats:title>\n                  <jats:p>Forty-one participants (mean age = 68.68 years) underwent MRI scanning and multi-plex plasma-based inflammatory marker quantification. Microstructural changes were quantified using Diffusion Weighted Imaging (DWI) metrics, including mean diffusivity (MD), radial diffusivity (RD), mean kurtosis (MK), and radial kurtosis (RK). Voxel-wise general linear models, and cluster-based models were used to examine associations between plasma-derived inflammatory markers and brain microstructure.<\/jats:p>\n                <\/jats:sec>\n                <jats:sec>\n                  <jats:title>RESULTS<\/jats:title>\n                  <jats:p>Higher TARC levels were associated with widespread increases in MD and RD across both gray and white matter, implicating reduced microstructural integrity and potential myelin disruption. In contrast, kurtosis-based metrics demonstrated more spatially selective and generally weaker associations, with MK and RK showing limited decreases primarily within white matter tracts. Cluster-level analyses confirmed the robustness of diffusivity findings and highlighted consistent effect sizes across multiple regions.<\/jats:p>\n                <\/jats:sec>\n                <jats:sec>\n                  <jats:title>DISCUSSION<\/jats:title>\n                  <jats:p>These findings suggest that elevated TARC is linked to early microstructural alterations detectable with diffusion MRI, with diffusivity metrics demonstrating greater sensitivity to inflammation-related changes than kurtosis measures in this cohort. This work underscores the importance of incorporating inflammatory biomarkers in neuroimaging studies of aging and highlights diffusion MRI as a promising tool for detecting early neurobiological signatures of AD\/ADRD risk in African American populations.<\/jats:p>\n                <\/jats:sec>","DOI":"10.64898\/2026.05.12.26353011","type":"posted-content","created":{"date-parts":[[2026,5,15]],"date-time":"2026-05-15T20:25:14Z","timestamp":1778876714000},"source":"Crossref","is-referenced-by-count":0,"title":["Peripheral TARC (CCL17) Levels Track Widespread Microstructural Vulnerability in Cognitively Unimpaired Older African Americans"],"prefix":"10.64898","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-6314-4074","authenticated-orcid":false,"given":"Soodeh","family":"Moallemian","sequence":"first","affiliation":[{"name":"School of Arts and Sciences, Center for Molecular and Behavioral Neuroscience, Rutgers University - Newark"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9335-7524","authenticated-orcid":false,"given":"Samira","family":"Raminfard","sequence":"additional","affiliation":[{"name":"Department of Psychiatry, University of Pittsburgh"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3498-8355","authenticated-orcid":false,"given":"Isha","family":"Mhatre-Winters","sequence":"additional","affiliation":[{"name":"Department of Physiology and Pharmacology, Isakson Center for Neurological Disease Research, University of Georgia, GA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0552-8464","authenticated-orcid":false,"given":"Miray","family":"Budak","sequence":"additional","affiliation":[{"name":"Center for Molecular and Behavioral Neuroscience, Rutgers University - 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