{"title":"Discovery of plasma biomarkers related to blood-brain barrier dysregulation in Alzheimer's disease.","authors":"Yuet Ruh Dan, Keng-Hwee Chiam","doi":"10.3389/fbinf.2024.1463001","DOIUrl":null,"url":null,"abstract":"<p><strong>Introduction: </strong>Blood-based biomarkers are quantitative, non-invasive diagnostic tools. This study aimed to identify candidate biomarkers for Alzheimer's 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.</p><p><strong>Methods: </strong>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.</p><p><strong>Results: </strong>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.</p><p><strong>Discussion: </strong>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.</p>","PeriodicalId":73066,"journal":{"name":"Frontiers in bioinformatics","volume":"4 ","pages":"1463001"},"PeriodicalIF":2.8000,"publicationDate":"2024-10-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11487119/pdf/","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Frontiers in bioinformatics","FirstCategoryId":"1085","ListUrlMain":"https://doi.org/10.3389/fbinf.2024.1463001","RegionNum":0,"RegionCategory":null,"ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"2024/1/1 0:00:00","PubModel":"eCollection","JCR":"Q2","JCRName":"MATHEMATICAL & COMPUTATIONAL BIOLOGY","Score":null,"Total":0}
引用次数: 0
Abstract
Introduction: Blood-based biomarkers are quantitative, non-invasive diagnostic tools. This study aimed to identify candidate biomarkers for Alzheimer's 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.
Methods: 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.
Results: 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.
Discussion: 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.
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