AD results from deposition of Aβ in the neocortex and HP-tau in the entorhinal cortex and hippocampus.52,53 More recent evidence suggests that even earlier HP-tau-related neurofibrillary changes may occur in the brainstem dorsal raphe nucleus or the locus ceruleus.54 In humans HP-tau pathology is associated with memory deficits,55 whereas Aβ deposition is not directly related to cognition,55 but shows topographical correspondence with the DMN.56 Moreover, the sequence of functional and structural disruption within and between DMN regions is reminiscent of the spread of tau pathology. Buckner et al. mapped in vivo PIB-PET Aβ deposition in patients with AD and cortical hubs in healthy controls and showed that regions of high Aβ deposition in patients largely overlap with DMN cortical hubs in the healthy brain, especially the posterior cingulate cortex.56 Disruption of DMN regions in AD has been consistently reported by resting-state fMRI studies using ICA or seed-based methods.57-61 Similar changes have been reported in subjects with mild cognitive impairment, a condition which is believed to often represent pre-clinical AD.62-64 Early DMN functional disruption in AD involves the medial temporal lobe
