The proposed model is most consistent with an age-based hypothesis of Alzheimer's disease that postulates three fundamental steps: initial injury aggravated by age, chronic neuroinflammation, and transition of most brain cells to a new state [8]. These key stages of the disease were independently observed and associated with transcriptional changes in our analysis of the brain transcriptome. We also identified a striking resemblance of the biological processes behind the disease progression biomarkers with epithelial-to-mesenchymal transition (EMT) [39]. The AD processes are most similar to EMT type 2, which is dependent on inflammation-inducing injuries for initiation and continued occurrence. Associated with tissue regeneration and organ fibrosis in kidney, lung, and liver, EMT type 2 generates mesenchymal cells that produce excessive amounts of extracellular matrix (ECM). Similarly, a transition of AD brain into a tissue enriched with mesenchymal cells produces a large amount of ECM containing β-amyloid. This model of the disease implies that multiple independent genetic factors, as well as infections and/or injuries may accelerate consecutive transitions leading to the disease. It also suggests different therapeutic strategies for early and late
