{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,1,27]],"date-time":"2026-01-27T20:50:37Z","timestamp":1769547037614,"version":"3.49.0"},"reference-count":73,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2024,10,4]],"date-time":"2024-10-04T00:00:00Z","timestamp":1728000000000},"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. Bioinform."],"abstract":"<jats:sec><jats:title>Introduction<\/jats:title><jats:p>Blood-based biomarkers are quantitative, non-invasive diagnostic tools. This study aimed to identify candidate biomarkers for Alzheimer\u2019s disease (AD) using publicly available omics datasets, using the hypothesis that with blood-brain barrier dysfunction in AD, brain-synthesized proteins can leak into plasma for detection.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Differential abundance results of plasma and brain proteomic datasets were integrated to obtain a list of potential biomarkers. Biological validity was investigated with intercellular communication and gene regulatory analyses on brain single-cell transcriptomics data.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Five proteins (APOD, B2M, CFH, CLU, and C3) fit biomarker criteria. 4 corresponding transcripts (APOD, B2M, CLU, and C3) were overexpressed in AD astrocytes, mediated by AD-related dysregulations in transcription factors regulating neuroinflammation. Additionally, CLU specifically induced downstream expression of neuronal death genes.<\/jats:p><\/jats:sec><jats:sec><jats:title>Discussion<\/jats:title><jats:p>In conclusion, a 5-protein panel is shown to effectively identify AD patients, with evidence of disease specificity and biological validity. Future research should investigate the mechanism of protein leakage through the blood-brain barrier.<\/jats:p><\/jats:sec>","DOI":"10.3389\/fbinf.2024.1463001","type":"journal-article","created":{"date-parts":[[2024,10,4]],"date-time":"2024-10-04T08:24:21Z","timestamp":1728030261000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":2,"title":["Discovery of plasma biomarkers related to blood-brain barrier dysregulation in Alzheimer\u2019s disease"],"prefix":"10.3389","volume":"4","author":[{"given":"Yuet Ruh","family":"Dan","sequence":"first","affiliation":[]},{"given":"Keng-Hwee","family":"Chiam","sequence":"additional","affiliation":[]}],"member":"1965","published-online":{"date-parts":[[2024,10,4]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"1083","DOI":"10.1038\/nmeth.4463","article-title":"SCENIC: single-cell regulatory network inference and clustering","volume":"14","author":"Aibar","year":"2017","journal-title":"Nat. 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