The spatial distribution of coupling between tau and neurodegeneration in amyloid- positive mild cognitive impairment

Synergies between amyloid-beta (A beta), tau, and neurodegeneration persist along the Alzheimer's disease (AD) continuum. This study aimed to evaluate the extent of spatial coupling between tau and neurodegeneration (atrophy) and its relation to A beta positivity in mild cognitive impairment (MCI). Data from 409 participants were included (95 cognitively normal controls, 158 A beta positive (A beta+) MCI, and 156 A beta negative (A beta-) MCI). Florbetapir PET, Flortaucipir PET, and structural MRI were used as biomarkers for A beta, tau and atrophy, respectively. Individual correlation matrices for tau load and atrophy were used to layer a multilayer network, with separate layers for tau and atrophy. A measure of coupling between corresponding regions of interest (ROIs) in the tau and atrophy layers was computed, as a function of A beta positivity. Fewer than 25% of the ROIs across the brain showed heightened coupling between tau and atrophy in A beta+, relative to A beta- MCI. Coupling strengths in the right rostral middle frontal and right paracentral gyri, in particular, mediated the association between A beta burden and cognition in this sample.