In vivo characterization of the early states of the amyloid-beta network

Alzheimer's disease is a neurodegenerative disease that is associated with the abnormal accumulation of amyloid-beta. Much is known about regional brain atrophy in Alzheimer's disease, yet our knowledge about the network nature of Alzheimer's disease-associated amyloid-beta accumulation is limited. We use stepwise connectivity analysis of Pittsburgh Compound B positron emission tomography images to reveal the network properties of amyloid-beta deposits in normal elderly subjects and clinical patients with Alzheimer's disease. We found that amyloid-beta accumulation in the medial temporal lobe is associated with accumulation in cortical regions such as orbitofrontal, lateral temporal and precuneus/posterior cingulate cortices in Alzheimer's disease. In normal subjects, there was a predominant association between amyloid-beta deposits in the hippocampus and the midline prefrontal/orbitofrontal regions, even in those with very low amyloid-beta burden. Moreover, the orbitofrontal cortex, amygdala nucleus and hippocampus exhibit hub properties in the amyloid-beta network that may be critical to understanding the putative spreading mechanisms of Alzheimer's disease pathology in early stages.