A hypothetical time course of biomarker abnormalities and pathological changes in AD is proposed based on the longitudinal measurements of (i) Aβ and P-tau in CSF or in the brain by positron emission tomography (PET), (ii) neurodegeneration using fluorodeoxyglucose (FDG)-PET (hypometabolism) and magnetic resonance imaging (MRI) (hippocampal atrophy), (iii) synaptic dysfunction using FDG-PET and functional MRI (fMRI), (iv) neuroinflammatory changes, and (v) mitochondrial dysfunction [8,30,45,53,54]. Here, MAPT is linked to Alzheimer disease.