{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,18]],"date-time":"2026-03-18T20:57:28Z","timestamp":1773867448483,"version":"3.50.1"},"reference-count":40,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2024,10,9]],"date-time":"2024-10-09T00:00:00Z","timestamp":1728432000000},"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><jats:title>Introduction<\/jats:title><jats:p>Early-onset Alzheimer\u2019s disease (EOAD) is sporadic, highly heterogeneous, and its underlying pathogenic mechanisms remain largely elusive. Proteomics research aims to uncover the biological processes and key proteins involved in disease progression. However, no proteomic studies to date have specifically focused on EOAD brain tissue.<\/jats:p><\/jats:sec><jats:sec><jats:title>Method<\/jats:title><jats:p>We integrated proteomic data from brain tissues of two Alzheimer\u2019s disease (AD) cohorts and constructed a protein co-expression network using weighted gene co-expression network analysis (WGCNA). We identified modules associated with EOAD, conducted functional enrichment analysis to understand the biological processes involved in EOAD, and pinpointed potential key proteins within the core modules most closely linked to AD pathology.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>In this study, we identified a total of 2,749 proteins associated with EOAD. Through protein co-expression network analysis, we discovered 41 distinct co-expression modules. Notably, the proteins within the core module most closely linked to AD pathology were significantly enriched in neutrophil degranulation. Additionally, we identified two potential key proteins within this core module that have not been previously reported in AD and validated their expression levels in 5xFAD mice.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>In summary, through a protein co-expression network analysis, we identified EOAD-related biological processes and molecular pathways, and screened and validated two key proteins, ERBB2IP and LSP1. These proteins may play an important role in the progression of EOAD, suggesting they could serve as potential therapeutic targets for the disease.<\/jats:p><\/jats:sec>","DOI":"10.3389\/fnagi.2024.1412222","type":"journal-article","created":{"date-parts":[[2024,10,9]],"date-time":"2024-10-09T04:55:36Z","timestamp":1728449736000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":3,"title":["Identification of key proteins in early-onset Alzheimer\u2019s disease based on WGCNA"],"prefix":"10.3389","volume":"16","author":[{"given":"Dazhi","family":"Li","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yaxin","family":"Wang","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jinliang","family":"Wang","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Qiqiang","family":"Tang","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1965","published-online":{"date-parts":[[2024,10,9]]},"reference":[{"key":"ref9001","doi-asserted-by":"publisher","first-page":"1449","DOI":"10.1093\/brain\/awab387","article-title":"VEGF signalling causes stalls in brain capillaries and reduces cerebral blood flow in Alzheimer\u2019s mice","volume":"145","author":"Ali","year":"2022","journal-title":"Brain"},{"key":"ref1","doi-asserted-by":"publisher","first-page":"975","DOI":"10.1016\/j.neuron.2019.12.015","article-title":"Deep multilayer brain proteomics identifies molecular networks in Alzheimer\u2019s disease progression","volume":"105","author":"Bai","year":"2020","journal-title":"Neuron"},{"key":"ref9002","doi-asserted-by":"publisher","first-page":"1286","DOI":"10.1016\/j.neurobiolaging.2014.01.003","article-title":"Migration of neutrophils targeting amyloid plaques in Alzheimer\u2019s disease mouse model","volume":"35","author":"Baik","year":"2014","journal-title":"Neurobiol. 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