AUTHOR=Dan Yuet Ruh , Chiam Keng-Hwee 

TITLE=Discovery of plasma biomarkers related to blood-brain barrier dysregulation in Alzheimer’s disease

JOURNAL=Frontiers in Bioinformatics

VOLUME=Volume 4 - 2024

YEAR=2024

URL=https://www.frontiersin.org/journals/bioinformatics/articles/10.3389/fbinf.2024.1463001

DOI=10.3389/fbinf.2024.1463001

ISSN=2673-7647

ABSTRACT=IntroductionBlood-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.MethodsDifferential 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.ResultsFive 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.DiscussionIn 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.