MAPT and Brain atrophy: The next stage of biomarker alteration include neuronal injury, shown by increased levels of CSF total tau protein (t-tau) and tau phosphorylated at threonine 181 (p-tau181/p-tau), and brain atrophy revealed by structural MRI, and synaptic loss and neurodegeneration detected by DTI or FDG-PET (Figures 2, 3; Shen et al., 2018).