Major imaging biomarkers of Alzheimer's disease include amyloid deposition 
[imaged with [(11)C]Pittsburgh compound B (PiB) PET], altered glucose metabolism 
(imaged with [(18)F]fluro-deoxyglucose PET), and structural atrophy (imaged by 
MRI). Recently we published the initial subset of imaging findings for specific 
regions in a cohort of individuals with autosomal dominant Alzheimer's disease. 
We now extend this work to include a larger cohort, whole-brain analyses 
integrating all three imaging modalities, and longitudinal data to examine 
regional differences in imaging biomarker dynamics. The anatomical distribution 
of imaging biomarkers is described in relation to estimated years from symptom 
onset. Autosomal dominant Alzheimer's disease mutation carrier individuals have 
elevated PiB levels in nearly every cortical region 15 y before the estimated 
age of onset. Reduced cortical glucose metabolism and cortical thinning in the 
medial and lateral parietal lobe appeared 10 and 5 y, respectively, before 
estimated age of onset. Importantly, however, a divergent pattern was observed 
subcortically. All subcortical gray-matter regions exhibited elevated PiB 
uptake, but despite this, only the hippocampus showed reduced glucose 
metabolism. Similarly, atrophy was not observed in the caudate and pallidum 
despite marked amyloid accumulation. Finally, before hypometabolism, a 
hypermetabolic phase was identified for some cortical regions, including the 
precuneus and posterior cingulate. Additional analyses of individuals in which 
longitudinal data were available suggested that an accelerated appearance of 
volumetric declines approximately coincides with the onset of the symptomatic 
phase of the disease.