{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,18]],"date-time":"2026-08-18T13:24:30Z","timestamp":1787059470014,"version":"build-2736575974"},"reference-count":90,"publisher":"SAGE Publications","issue":"4","license":[{"start":{"date-parts":[[2026,1,7]],"date-time":"2026-01-07T00:00:00Z","timestamp":1767744000000},"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":[[2026,2]]},"abstract":"<jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Alzheimer's disease (AD) is a progressive neurodegenerative disorder characterized by cognitive decline, memory loss and neuronal dysfunction. While amyloid-\u03b2 plaques and tau tangles remain central to AD pathology, emerging evidence implicates ferroptosis, an iron-dependent, regulated form of cell death marked by lipid peroxidation and oxidative stress, as a critical contributor to disease progression.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Objective<\/jats:title>\n                    <jats:p>This study investigates the interplay between major AD risk factors including chronic alcoholism, alcohol-nicotine co-abuse, aging, genetic predisposition, comorbidities and lifestyle habits and ferroptosis-related molecular pathways.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>GEO datasets and 115 ferroptosis-related genes were analyzed using z-score\/FDR and Limma, followed by GO\/KEGG\/GSEA enrichment, machine-learning\u2013based gene selection with ROC-AUC validation, immune-cell profiling using CIBERSORT, and hub gene\u2013miRNA network construction via NetworkAnalyst.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      Our findings demonstrate that these risk factors converge on shared mechanisms involving iron dysregulation, oxidative stress and lipid imbalance which are hallmarks of ferroptosis. We identified seven ferroptosis-associated biomarker genes CYBB, FERMT1, BAX, SOD1, ACSL4, TP53, and FTH1 as being significantly dysregulated in AD. Integrative gene-miRNA interaction analysis revealed several hub miRNAs including hsa-miR-34a (TP53, SOD1, BAX), hsa-miR-34b and hsa-miR-34c (TP53, FERMT1), hsa-miR-125a-5p (FERMT1, TP53) and hsa-miR-20a-5p (ACSL4, BAX) suggesting a network of coordinated post-transcriptional regulation. Additionally, we observed strong neuroinflammatory signatures in AD with increased infiltration of pro-inflammatory macrophages (M1), CD8\n                      <jats:sup>+<\/jats:sup>\n                      T cells, monocytes and neutrophils. This heightened immune activity may be exacerbated by ferroptotic cell death and associated oxidative stress forming a vicious cycle of neurodegeneration. Finally, we propose glutathione and alpha-tocopheral (vitamin E) as potential therapeutic compounds due to their antioxidative role in preventing ferroptosis.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>Overall, our study provides novel insights into the mechanistic connections between ferroptosis, miRNA regulation, immune responses and AD pathology highlighting potential biomarkers and therapeutic targets.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1177\/13872877251411331","type":"journal-article","created":{"date-parts":[[2026,1,7]],"date-time":"2026-01-07T14:01:01Z","timestamp":1767794461000},"page":"1834-1857","update-policy":"https:\/\/doi.org\/10.1177\/sage-journals-update-policy","source":"Crossref","is-referenced-by-count":0,"title":["Unraveling the impact of risk factors on the ferroptosis-Alzheimer's disease link for early 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