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

Abstract

ABSTRACTSynergies 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 subjects 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/nodes in the tau and atrophy layers was computed, as a function of Aβ positivity. The extent to which tau-atrophy coupling mediated associations between Aβ burden and cognitive decline was also evaluated. Heightened coupling between tau and atrophy in Aβ+ MCI was found primarily in the entorhinal and hippocampal regions (i.e., in regions corresponding to Braak stages I/II), and to a lesser extent in limbic and neocortical regions (i.e., corresponding to later Braak stages). Coupling strengths in the right middle temporal and inferior temporal gyri mediated the association between Aβ burden and cognition in this sample. Higher coupling between tau and atrophy in Aβ+ MCI is primarily evident in regions corresponding to early Braak stages and relates to overall cognitive decline. Coupling in neocortical regions is more restricted in MCI.