{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,23]],"date-time":"2026-07-23T15:52:19Z","timestamp":1784821939314,"version":"3.55.0"},"reference-count":77,"publisher":"SAGE Publications","issue":"3","license":[{"start":{"date-parts":[[2025,5,2]],"date-time":"2025-05-02T00:00:00Z","timestamp":1746144000000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.sagepub.com\/page\/policies\/text-and-data-mining-license"}],"content-domain":{"domain":["journals.sagepub.com"],"crossmark-restriction":true},"short-container-title":["Journal of Alzheimer\u2019s Disease"],"published-print":{"date-parts":[[2025,6]]},"abstract":"<jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>DNA damage and repair (DDR) and structural atrophies in different brain regions were recognized as critical factors in the onset of Alzheimer's disease (AD).<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Objective<\/jats:title>\n                    <jats:p>We utilized Mendelian randomization (MR) to examine the causal effects of the DDR-related molecular traits on AD and the potential mediating roles of different brain region volumes.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>In primary analysis, we utilized public genome-wide association studies of AD and summary data from existing molecular traits datasets, including gene expression, DNA methylation, and protein levels quantitative trait loci (eQTL, mQTL, and pQTL) in both blood and brain to examine their causal associations by summary-data-based MR analysis and additional five two-sample MR methods. Subsequently, mediation analysis explored the potential mediate roles of 13 imaging-derived brain volume phenotypes in the associations between the DDR pathways and AD through a network MR design.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>We found that the volumes of the right thalamus proper and global cerebral white matter mediated the causal pathways from EGFR to AD and relatively weak mediation effects of the right lateral ventricle volume in the causal pathways involving CHRNE, DNTT, and AD.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>We identified causal relationships among DDR pathways, specific brain region volumes, and AD. Monitoring the molecular traits of these DDR-related genes and developing targeted drugs may help detect and interrupt the early progression of AD.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1177\/13872877251333811","type":"journal-article","created":{"date-parts":[[2025,5,2]],"date-time":"2025-05-02T07:52:15Z","timestamp":1746172335000},"page":"1017-1029","update-policy":"https:\/\/doi.org\/10.1177\/sage-journals-update-policy","source":"Crossref","is-referenced-by-count":1,"title":["Identifying the mediating role of brain atrophy on the relationship between DNA damage repair pathway and Alzheimer's disease: A Mendelian randomization analysis and mediation analysis"],"prefix":"10.1177","volume":"105","author":[{"given":"Wei","family":"Bao","sequence":"first","affiliation":[{"name":"Department of Rehabilitation Medicine, The First Affiliated Hospital, Jiangxi Medical College, Nanchang University, Nanchang, Jiangxi Province, China"},{"name":"Department of Pediatrics, The First 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