A Qualitative Analysis Based on Relative Expression Orderings Identifies Transcriptional Subgroups for Alzheimer's Disease

Abstract

Background: Alzheimer's disease (AD) is a heterogeneous neurodegenerative disease. However, few studies have investigated the heterogeneous gene expression patterns in AD.

Objective and methods: We examined the gene expression patterns in four brain regions of AD based on the within-sample relative expression orderings (REOs). Gene pairs with significantly reversed REOs in AD samples compared to non-AD controls were identified for each brain region using Fisher's exact test, and filtered according to their transcriptional differences between AD samples. Subgroups of AD were classified by cluster analysis.

Results: REO-based gene expression profiling analyses revealed that transcriptional differences, as well as distinct disease subsets, existed within AD patients. For each brain region, two main subgroups were classified: one subgroup reported differentially expressed genes overlapped with the age-related genes, and the other was related to neuroinflammation.

Conclusion: AD transcriptional subgroups might help understand the underlying pathogenesis of AD, and lend support to a personalized approach to AD management.

Keywords: Alzheimer’s Disease; aging; gene expression; neuroinflammation; relative expression orderings; transcriptional subgroups..