The second largest disease-specific pattern (Alz) contained genes associated with cell adhesion, migration, and morphogenesis. This metagene prominently featured genes characteristic of epithelial-to-mesenchymal transition (EMT), such as VIM, TWIST1, and FN1 [39], (Fig. S4). The connection of Alz with EMT suggests a major transformation in brain tissue physiology including changes in receptor signaling, growth factor dependence, and cell adhesion during the disease. Considering that the third disease-specific biomarker, Inflame, reflects chronic neuroinflammation [7], [40], it is hard to ignore the similarity between AD with other examples of EMT type 2, such as tissue fibrosis, where chronic inflammation and upregulation of TGFB2 contribute to pathogenesis [39]. The levels of Alz in AD are much higher than in unaffected brain regions or in the PFC in HD, suggesting that these gene expression changes are not generally reflecting neurodegeneration, but relate to AD pathology.
