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

Synergies between amyloid-β (Aβ), 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 Aβ positivity in mild cognitive impairment (MCI). Data from 409 participants were included (95 cognitively normal controls, 158 Aβ positive (Aβ+) MCI, and 156 Aβ negative (Aβ-) MCI). Florbetapir PET, Flortaucipir PET, and structural MRI were used as biomarkers for Aβ, 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 Aβ positivity. Fewer than 25% of the ROIs across the brain showed heightened coupling between tau and atrophy in Aβ+ , relative to Aβ- MCI. Coupling strengths in the right rostral middle frontal and right paracentral gyri, in particular, mediated the association between Aβ burden and cognition in this sample.