An integrative network analysis to identify potential blood biomarkers of Alzheimer’s disease: a meta-analysis

Abstract

Alzheimer’s disease (AD), accounting for around 70% of all dementia, affects approximately 24.3 million people worldwide. Although many researchers have attempted to develop compromising medicines, there is no definite medication for AD. Current clinically used medications do not prevent AD progression or achieve permanent relief but they only affect slow down disease progression. Due to these reasons, an interest in the development of early AD diagnostic biomarkers has actively increased. Although numerous AD biomarkers, including cerebrospinal fluid (CSF) and neuroimaging biomarkers, are already clinically used during the last 20 years, researchers recently attempt to develop and validate blood biomarker of AD due to its advantages: less invasive, highly accessible and inexpensive. Therefore, I performed a systemic search of reported articles published in from 1990 to January 2013 using PubMed. After three filtering steps of the 864 studies that was initially searched, 75 articles accompanying with 97 blood biomarkers (BBs) that were finally included in my study. Following meta-scoring of each BB with designated criteria was performed. The highest meta-scored BB was CRP with pattern of increase (meta-score: 62) followed by CD40 which meta-score was 59. Assuming that correlation between BBs and AD-Related genes (ADRs) from the OMIM data would provide significant insight into discovery of potential blood biomarker candidates, I performed the protein-protein interaction (PPI) network analysis along with enrichment analysis. In the BB-PPI, 49 proteins are linked via 78 edges was observed. In addition, 132 proteins are connected via 344 edges and 54 linker molecules, potential blood biomarkers in extended PPI network. In this study, I suggest rationally ascendant BBs as AD diagnostic marker among reported BBs through designated meta-scoring system. Also, potential blood biomarker candidates along with their functional roles in AD pathogenesis are suggested by int...