In Vivo Tau, Amyloid, and Gray Matter Profiles in the Aging Brain.

UNLABELLED: We provide a comparative in vivo examination of the brain network-based distribution of two hallmarks of Alzheimer's disease (AD) pathology in cognitively normal individuals: (1) Tau, detected with a novel positron emission tomography (PET) tracer known as (18)F-AV-1451; and (2) amyloid-β, quantified with (11)C-PiB PET. We used a high-resolution graph-based approach to investigate local-to-local and local-to-distributed cortical associations between the maps of Tau, amyloid-β, and gray matter intensity. Our study shows that Tau and amyloid-β deposits are associated with distinctive spatial patterns of brain tissue loss. Moreover, Tau and amyloid-β accumulations have strong network interdigitations in heteromodal and associative areas of the cortical mantle, particularly the inferior-lateral temporal lobe. These findings contribute significantly to our understanding of how these two main hallmarks of AD pathology propagate across the elderly human brain.

SIGNIFICANCE STATEMENT: It has been postulated that Alzheimer's disease (AD) pathology interacts and resides within system-level circuits of the human brain, long before the onset of cognitive symptoms. However, a side-by-side comparison of tissue loss, amyloid-β, and Tau deposition in early stages of the disease has been precluded until the recent advent of Tau tracer-based neuroimaging. In this study, we used Tau positron emission tomography and network analyses to disentangle these pathological relationships. We found that Tau and amyloid-β deposits are associated with distinctive spatial patterns of brain tissue loss. Moreover, we uncovered the network interdigitations of Tau and amyloid-β in the cortical mantle. These findings contribute significantly to our understanding of how two main hallmarks of AD pathology propagate across the elderly human brain.