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ORIGINAL RESEARCH article

Front. Bioinform.
Sec. Integrative Bioinformatics
Volume 4 - 2024 | doi: 10.3389/fbinf.2024.1463001

Discovery of Plasma Biomarkers Related to Blood-Brain Barrier Dysregulation in Alzheimer's Disease

Provisionally accepted
Yuet Ruh Dan Yuet Ruh Dan 1,2Keng-Hwee Chiam Keng-Hwee Chiam 1,2*
  • 1 Bioinformatics Institute (A*STAR), Singapore, Singapore
  • 2 School of Biological Sciences, College of Science, Nanyang Technological University, Singapore, Singapore

The final, formatted version of the article will be published soon.

    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. 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. 5 proteins (APOD, B2M, CFH, CLU, C3) fit biomarker criteria. 4 corresponding transcripts (APOD, B2M, CLU, 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. 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.

    Keywords: Alzheimer's disease, Plasma biomarkers, Blood-Brain Barrier, proteomics analysis, Single-cell transcriptomics

    Received: 11 Jul 2024; Accepted: 19 Sep 2024.

    Copyright: © 2024 Dan and Chiam. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

    * Correspondence: Keng-Hwee Chiam, Bioinformatics Institute (A*STAR), Singapore, 138632, Singapore

    Disclaimer: All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article or claim that may be made by its manufacturer is not guaranteed or endorsed by the publisher.