We also describe three other distinct disease-specific patterns. The NdStress biomarker, which contained both up- and downregulated genes, dominated differential expression between AD and non-demented brains matched for BioAge score. The upregulated genes contained multiple heatshock and proteasome proteins. Activation of these pathways may reflect the response to disease-related stress. Another set of genes in this module are cell cycle genes indicative of cell cycle arrest or apoptosis. The downregulated arm of NdStress is enriched in one-carbon/folate metabolism genes and could underlay the perturbations in these metabolic pathways, which are among the earliest biomarkers associated with neurodegenerative disorders including AD [34], [35], [36].
