from N0 to N1. The following upregulation of the Inflame biomarker is associated with transition from N1 to N2. The brains in these states were diagnosed as normal because the subjects did not yet exhibit any cognitive impairment associated with AD. The next transition, from N2 to A1, is associated with massive disruptions in metabolic pathways and marked acceleration of aging follows. Some brains, however, avoid transitioning to A1 and continue to age into N3. Another transition to AD state A2 can happen later, since we observe brains with high scores for both NdStress and Alz, which may be associated with a different path to AD. Alternatively, A2 is possibly localized to a brain region not covered in the dataset. This transition may, therefore, appear later than A1 in a particular brain region and happen much earlier in some other brain region.
