The investigations of Benzinger et al. suggest there are regional differences in the brain in amyloid deposition, hypometabolism, and atrophy and that not all regions of atrophy show reduced metabolism even in the presence of amyloid deposition [46], illustrating the difficulty in comprehending the pathophysiology of AD, and underpinning the importance of amyloid deposition in the pathophysiology of sporadic YOAD which, in the future, will be aided by the application of tau and microglial activation markers using PET imaging in longitudinal studies [47]. Here, MAPT is linked to Alzheimer disease.