{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,14]],"date-time":"2026-04-14T12:46:23Z","timestamp":1776170783194,"version":"3.50.1"},"reference-count":62,"publisher":"Wiley","issue":"12","license":[{"start":{"date-parts":[[2025,12,21]],"date-time":"2025-12-21T00:00:00Z","timestamp":1766275200000},"content-version":"vor","delay-in-days":20,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"},{"start":{"date-parts":[[2025,12,1]],"date-time":"2025-12-01T00:00:00Z","timestamp":1764547200000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Health Science Reports"],"published-print":{"date-parts":[[2025,12]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background and Aims<\/jats:title>\n                    <jats:p>Alzheimer's disease (AD) is a progressive neurodegenerative disorder characterized by early microstructural white matter (WM) damage, often preceding clinical symptoms. While cerebrospinal fluid (CSF) biomarkers provide valuable insights into AD pathology, they are invasive and may not reflect early WM changes. U\u2010p53AZ, a conformational variant of p53 detected via the AlzoSure\u00ae blood assay, has emerged as a potential biomarker for early AD detection. This study aimed to investigate the association between AlzoSure\u00ae prediction scores and WM microstructural integrity in cognitively normal (CN) individuals and those with mild cognitive impairment (MCI), using diffusion tensor imaging (DTI). Secondary analyses explored parallels with established CSF biomarkers (A\u03b2\u2081\u208b\u2084\u2082, total tau, and p\u2010tau181).<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>We analyzed data from 106 Alzheimer's Disease Neuroimaging Initiative (ADNI) participants (46 CN, 60 MCI) with available DTI and biomarker data. AlzoSure\u00ae scores were derived from plasma samples using immunoprecipitation. DTI metrics (fractional anisotropy, mean, axial, and radial diffusivity) were extracted from atlas\u2010defined WM regions. Linear regression models, stratified by diagnosis and adjusted for age, gender, and polygenic hazard score, were used to examine associations between biomarkers and DTI indices. False discovery rate (FDR) correction was applied for multiple comparisons.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>In the MCI group, higher AlzoSure\u00ae scores were significantly associated with reduced diffusivity metrics in the left cingulum hippocampal bundle, a region implicated in early AD\u2010related disconnection. Parallel associations were observed with CSF t\u2010tau and p\u2010tau181 across other WM tracts in MCI. However, no associations remained significant after FDR adjustment.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>These findings underscore the potential of U\u2010p53AZ, as measured by AlzoSure\u00ae, to capture early WM microstructural alterations particularly in individuals with MCI, aligning with tau\u2010related pathology patterns. While exploratory, the results highlight U\u2010p53AZ as a non\u2010invasive candidate biomarker for early AD\u2010related neurodegeneration. Larger, longitudinal studies are needed to validate its diagnostic and prognostic utility in preclinical and prodromal AD stages.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/hsr2.71671","type":"journal-article","created":{"date-parts":[[2025,12,22]],"date-time":"2025-12-22T05:10:18Z","timestamp":1766380218000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Association Between U\u2010p53AZ Blood Biomarker and White Matter Microstructure in Early Alzheimer's Disease: A Cross\u2010Sectional Study Using AlzoSure\u00ae Predict"],"prefix":"10.1002","volume":"8","author":[{"given":"Hamide","family":"Nasiri","sequence":"first","affiliation":[{"name":"Student Research Committee, School of Medicine Zanjan University of Medical Science Zanjan Iran"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9236-8528","authenticated-orcid":false,"given":"Setayesh","family":"Farahani","sequence":"additional","affiliation":[{"name":"Cardiovascular Surgery Research and Development Committee Iran University of Medical Sciences (IUMS) Tehran Iran"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mehrdad","family":"Mozafar","sequence":"additional","affiliation":[{"name":"School of Medicine Tehran University of Medical Sciences Tehran Iran"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9722-0736","authenticated-orcid":false,"given":"Yasaman","family":"Ghiasi","sequence":"additional","affiliation":[{"name":"Faculty of Medicine Qazvin University of Medical Sciences Qazvin Iran"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Atousa Moghadam","family":"Fard","sequence":"additional","affiliation":[{"name":"Universal Scientific Education and Research Network (USERN) Tehran Iran"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Nasim","family":"Naseri","sequence":"additional","affiliation":[{"name":"Department of Animal Sciences and Biotechnology Faculty of Life Sciences and Biotechnology, Shahid Beheshti University Tehran Iran"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Amirhossein","family":"Khodadadi","sequence":"additional","affiliation":[{"name":"School of Medicine Mashhad University of Medical Sciences Mashhad Iran"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2345-8642","authenticated-orcid":false,"given":"Ali Salimi","family":"Asl","sequence":"additional","affiliation":[{"name":"Faculty of Medicine Student Research Committee, Hormozgan, University of Medical Sciences Bandar Abbas Iran"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Maryam","family":"Mirzapour","sequence":"additional","affiliation":[{"name":"Department of Mathematics Education Farhangian University Tehran Iran"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hossein","family":"Hamidi","sequence":"additional","affiliation":[{"name":"Department of Emergency Medicine Ahvaz Jundishapour University of Medical Sciences Ahvaz Iran"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Fatemeh","family":"Jafarirazi","sequence":"additional","affiliation":[{"name":"Department of Nuclear and Medical Radiation Engineering Sciences and Research Branch of Islamic Azad University Tehran Iran"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Navid","family":"Dinarvand","sequence":"additional","affiliation":[{"name":"Faculty of Electrical, Biomedical and Mechatronics Engineering Islamic Azad University Qazvin Iran"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2025,12,21]]},"reference":[{"key":"e_1_2_12_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.nrl.2016.02.016"},{"key":"e_1_2_12_3_1","doi-asserted-by":"publisher","DOI":"10.2147\/IJN.S200490"},{"key":"e_1_2_12_4_1","unstructured":"C.Patterson World Alzheimer Report2018. 2018; 00."},{"key":"e_1_2_12_5_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jalz.2019.01.010"},{"key":"e_1_2_12_6_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jalz.2018.02.001"},{"key":"e_1_2_12_7_1","doi-asserted-by":"publisher","DOI":"10.14283\/jpad.2021.15"},{"key":"e_1_2_12_8_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.mcna.2018.10.009"},{"key":"e_1_2_12_9_1","doi-asserted-by":"publisher","DOI":"10.3390\/molecules25245789"},{"key":"e_1_2_12_10_1","doi-asserted-by":"publisher","DOI":"10.1074\/mcp.RA118.001290"},{"key":"e_1_2_12_11_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.drudis.2022.01.016"},{"key":"e_1_2_12_12_1","article-title":"Pathogenesis of Alzheimer's Disease","volume":"1","author":"Rostagno A. 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