Between-networks hyperconnectivity is induced by beta-amyloid and may facilitate tau spread

Abstract

ABSTRACTAlzheimer’s disease (AD) is characterized by the buildup of neurofibrillary tau tangles and beta-amyloid (Aβ) plaques. While it has been hypothesized that Aβ facilitates the spread of tau outside of the medial temporal lobe (MTL), the specific pathological processes and mechanisms by which this occurs remain poorly understood. Our study employed advanced neuroimaging techniques, integrating 18F-Florbetaben Aβ and 18F-MK6240 tau positron emission tomography (PET) with resting-state functional magnetic resonance imaging (rs-fMRI) to characterize these mechanisms in two distinct datasets, that included 481 healthy elderly subjects, 46 of whom came with longitudinal data. Our research highlighted an intricate internetwork relationship between Aβ and tau accumulation, across spatially distinct functional networks. Additionally, we observed compelling evidence supporting the existence of a compensatory mechanism triggered by Aβ accumulation, resulting in hyperconnectivity between functional networks. Finally, the longitudinal findings indicate that between-networks hyperconnectivity is associated with future tau elevation and mediates the relationship between cortical Aβ and early-stage tau. Understanding this early brain alteration in response to the accumulation of Aβ could guide treatments early in the disease course and potentially prevent future tau accumulation.