{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,22]],"date-time":"2026-04-22T06:49:26Z","timestamp":1776840566159,"version":"3.51.2"},"reference-count":45,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,4,22]],"date-time":"2026-04-22T00:00:00Z","timestamp":1776816000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Aging Neurosci."],"abstract":"<jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Plasma phosphorylated tau at threonine 217 (p-Tau217) has emerged as a highly sensitive and specific blood-based biomarker for Alzheimer\u2019s Disease (AD). However, its regional brain correlates with multimodal neuroimaging, beyond tau-PET, remain underexplored, particularly in early disease phases where limbic involvement may predominate. This study aimed to map the associations of plasma p-Tau217 with amyloid-PET burden, FDG-PET metabolism, and structural brain morphometry in a well-characterized cohort spanning cognitively unimpaired (CU) and cognitively impaired (CI) individuals across AD dementia stages, hypothesizing increased AD neuroimaging biomarkers in individuals with elevated p-Tau217.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>We analyzed data from 259 participants from the University of Kansas Alzheimer\u2019s Disease Research Center (KU ADRC) Clinical Cohort. Imaging outcomes included amyloid-PET, FDG-PET, gray matter volumetric regions of interest as well as whole brain voxel-based morphometry (VBM), and surface-based morphometry (SBM) for cortical thickness (CT), sulcal depth (SD), gyrification index (GI), fractal dimension (FD). Analyses were stratified by diagnostic and pTau-217 positivity (CU pTau + , CU pTau -, CI pTau + and CI pTau-). Spearman\u2019s correlations and voxel\/surface-wise regressions evaluated p-Tau217 associations with imaging metrics, accounting for age and sex.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>Plasma p-Tau217 was elevated in CI versus CU. Individuals with elevated plasma p-Tau217 had increased amyloid-PET deposition across the cortex, as well as significantly higher centiloids, both in CU and CI individuals. In CI individuals, elevated p-Tau217 was associated with reduced voxel-wise gray matter volume and cortical thickness in limbic, temporal, parietal, and frontal regions, plus increased cingulate FD. In both CU and CI pTau + individuals, p-Tau217 correlated with AD Signature gray matter decreases.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>These findings show that CU and CI individuals with elevated plasma p-Tau217 have both increased amyloid-PET burden but also temporolimbic gray matter atrophy and hypometabolism. This supports p-Tau217 as a minimally invasive, scalable biomarker for early AD detection, risk stratification, and prognostic monitoring in preclinical stages, potentially guiding trial enrichment and personalized interventions.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fnagi.2026.1748524","type":"journal-article","created":{"date-parts":[[2026,4,22]],"date-time":"2026-04-22T05:51:00Z","timestamp":1776837060000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["Limbic-predominant neuroimaging correlates of plasma p-Tau217 in preclinical and clinical Alzheimer\u2019s disease"],"prefix":"10.3389","volume":"18","author":[{"given":"Ankit","family":"Patel","sequence":"first","affiliation":[{"name":"University of Kansas Alzheimer\u2019s Disease Research Center, University of Kansas Medical Center","place":["Kansas City, KS, United States"]},{"name":"Department of Neurology, University of Kansas School of 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Medical Center","place":["Kansas City, KS, United States"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Casey S.","family":"John","sequence":"additional","affiliation":[{"name":"University of Kansas Alzheimer\u2019s Disease Research Center, University of Kansas Medical Center","place":["Kansas City, KS, United States"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Dinesh Pal","family":"Mudaranthakam","sequence":"additional","affiliation":[{"name":"University of Kansas Alzheimer\u2019s Disease Research Center, University of Kansas Medical Center","place":["Kansas City, KS, United States"]},{"name":"Department of Biostatistics and Data Science, University of Kansas Medical Center","place":["Kansas City, KS, United States"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Heather M.","family":"Wilkins","sequence":"additional","affiliation":[{"name":"University of Kansas Alzheimer\u2019s Disease Research Center, University of Kansas 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