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

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.