The Significance of Lysosome in the Diagnosis and Subclassification of Alzheimer’s Disease

Abstract

Lysosomes are the main degradation organelles in eukaryotic cells, and their dysfunction is closely related to Alzheimer’s disease (AD). Our goal is to identify the lysosomal molecular subtype of AD and explore the mechanisms. By differential analysis, 50 differentially expressed lysosomal genes in AD were identified. R-package “ROCR” was used to calculate ROC curves and AUC values for lysosomal genes. “ConsensusClusterPlus” was used for consistent clustering of the AD data set. The contents of 28 kinds of immune cells in AD samples were calculated using the R-package “GSVA”. The R package “limma” was used to analyze the differences of autophagy genes. R package “WGCNA” carried out weighted co-expression network analysis. Two lysosomes subtypes were identified in AD cohort by lysosome diagnostics molecular, known as cluster 1/2. The results showed that 13 immune cells were significantly different between cluster 1 and cluster 2. A total of 76 differentially autopaghy genes were identified. The enrichment analysis showed that the key module genes were mainly concentrated in the synapses. We identified two subtypes based on lysosome gene expressions, preliminarily revealing that the heterogeneity of AD may be mainly caused by lysosomes. The role of lysosomes may be related to autophagy and synapses.