Exploring Biomarkers Related to Autophagy in Alzheimer's Disease Based on Pathway Crosstalk Analysis

Abstract The pathological mechanism of Alzheimer's disease (AD) involves multiple pathways, and the crosstalk between autophagy and other pathways plays an increasingly prominent role in AD. However, current methods are primarily based on single-gene analysis or a single signal pathway to find therapeutic targets for AD, which are somewhat limited. The aim of our study is to identify autophagy-related biomarkers in AD based on the crosstalk between autophagy and other pathways. The pathway analysis method (PAGI) was applied to find the feature mRNAs involved in the crosstalk between autophagy and many other AD-related pathways. Then, the weighted gene co-expression network analysis (WGCNA) was used to construct a co-expression module of feature mRNAs and differential lncRNAs. Finally, clinical information was used to screen the biomarkers related to the prognosis of AD in the co-expressed gene modules. The experiment finally identified 8 mRNAs and 2 lncRNAs (TLN1, ARRB1, FZD4, AKT1, JMJD7-PLA2G4B, STAT5A, SMAD7, ZNF274; AC113349.1, AC015878.2) as biomarkers of AD, and they all interact directly or indirectly with autophagy. In summary, we provide an effective method for extracting autophagy-related biomarkers based on pathway crosstalk in AD. This method enriches the therapeutic targets of AD and provides new insights into the molecular mechanism of autophagy in AD.