Alzheimer's disease (AD) is a complex disease, and numerous cellular events may be involved in etiology. RNAseq-based transcriptome data hold multilayer information content, which could be crucial in unraveling molecular mysteries of AD. It enables quantification of gene expression levels, identification of genomic variants, and elucidation of splicing anomalies such as exon skipping and intron retention. Additional integration of this information into protein-protein interaction networks and genome-scale metabolic models from the literature has potential to decipher functional modules and affected mechanisms for complex scenarios such as AD. In this chapter, we review the application areas of the multilayer content of RNAseq and associated integrative approaches available, with a special focus on AD.