{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,21]],"date-time":"2026-08-21T12:01:12Z","timestamp":1787313672457,"version":"build-2736575974"},"reference-count":68,"publisher":"MDPI AG","issue":"11","license":[{"start":{"date-parts":[[2025,11,13]],"date-time":"2025-11-13T00:00:00Z","timestamp":1762992000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Major and Special Projects of Fujian Province","award":["2020NZ010008"],"award-info":[{"award-number":["2020NZ010008"]}]},{"name":"High-level Talent Innovation and Entrepreneurship Project of Quanzhou","award":["2022C006R"],"award-info":[{"award-number":["2022C006R"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Genes"],"abstract":"<jats:p>Background: Alzheimer\u2019s disease (AD) is a progressive neurodegenerative disorder with unclear pathogenic mechanisms. Dysregulated zinc metabolism contributes to AD pathology. This study aimed to identify zinc metabolism-related hub genes to provide potential biomarkers and therapeutic targets for AD. Methods: We performed an integrative analysis of multiple transcriptomic datasets from AD patients and normal controls. Differentially expressed genes and weighted gene co-expression network analysis (WGCNA) were combined to identify hub genes. We then conducted Gene Set Enrichment Analysis (GSEA), immune cell infiltration analysis (CIBERSORT), and receiver operating characteristic (ROC) curve analysis to assess the hub gene\u2019s biological function, immune context, and diagnostic performance. Drug-gene interactions were predicted using the DrugBank database. Results: We identified a single key zinc transporter\u2013related hub gene, SLC30A3, which was significantly downregulated in AD and demonstrated potential diagnostic value (AUC 0.70\u20130.80). Lower SLC30A3 expression was strongly associated with impaired synaptic plasticity (long-term potentiation, long-term depression, calcium signaling pathway, and axon guidance), mitochondrial dysfunction (the citrate cycle and oxidative phosphorylation), and pathways common to major neurodegenerative diseases (Parkinson\u2019s disease, AD, Huntington\u2019s disease, and amyotrophic lateral sclerosis). Furthermore, SLC30A3 expression correlated with specific immune infiltrates, particularly the microglia-related chemokine CX3CL1. Zinc chloride and zinc sulfate were identified as potential pharmacological modulators. Conclusions: Our study systematically identifies SLC30A3 as a novel biomarker in AD, linking zinc dyshomeostasis to synaptic failure, metabolic impairment, and neuroimmune dysregulation. These findings offer a new basis for developing targeted diagnostic and therapeutic strategies for AD.<\/jats:p>","DOI":"10.3390\/genes16111380","type":"journal-article","created":{"date-parts":[[2025,11,13]],"date-time":"2025-11-13T12:57:13Z","timestamp":1763038633000},"page":"1380","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["SLC30A3 as a Zinc Transporter-Related Biomarker and Potential Therapeutic Target in Alzheimer\u2019s Disease"],"prefix":"10.3390","volume":"16","author":[{"given":"Ruyu","family":"Bai","sequence":"first","affiliation":[{"name":"School of Medicine, Huaqiao University, Quanzhou 362021, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhiyun","family":"Cheng","sequence":"additional","affiliation":[{"name":"School of Medicine, Huaqiao University, Quanzhou 362021, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0633-1906","authenticated-orcid":false,"given":"Yong","family":"Diao","sequence":"additional","affiliation":[{"name":"School of Medicine, Huaqiao University, Quanzhou 362021, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,11,13]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"413","DOI":"10.1016\/S0140-6736(20)30367-6","article-title":"Dementia prevention, intervention, and care: 2020 report of the Lancet Commission","volume":"396","author":"Livingston","year":"2020","journal-title":"Lancet"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"1025","DOI":"10.1007\/s12264-021-00701-z","article-title":"Comprehensive Management of Daily Living Activities, behavioral and Psychological Symptoms, and Cognitive Function in Patients with Alzheimer\u2019s Disease: A Chinese Consensus on the Comprehensive Management of Alzheimer\u2019s Disease","volume":"37","author":"Jia","year":"2021","journal-title":"Neurosci. 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