MAPT and Alzheimer disease: It is plausible that atrophy in AD occurs in 2 phases: subtle atrophy following Aβ+, possibly mediated by increases in glial activation38 or prefilamentous tau hyperphosphorylation in distant, tangle-bearing regions,39,40 followed by stronger atrophy with longer Aβ+ duration and the onset of NFT pathology in these ROIs.