Resting-state global brain activity affects early β-amyloid accumulation and hypoconnectivity in default mode network

The β-amyloid (Aβ) plaque, an Alzheimer’s disease (AD) hallmark, accumulates first in the default mode network (DMN) regions years before AD diagnosis. The underlying mechanisms remain elusive. Low-frequency (<0.1 Hz) resting-state global brain activity was recently found coupled by cerebrospinal fluid (CSF) movements, and this coupling has been linked to AD pathologies, including Aβ accumulations, presumably due to its role in glymphatic clearance. Here we showed the preferential Aβ accumulation in DMN was related to the reduced engagement of the global brain activity in these regions, partly explained by its failure to reach these regions as cortical propagating waves.