The default mode network exhibits circuit-specific selective vulnerability despite widespread amyloid burden in an animal model of Alzheimer’s disease

In Alzheimer’s Disease (AD) the default mode network (DMN) exhibits selective vulnerability to functional decline and amyloid beta (Aβ) plaques in early AD. DMN vulnerability may simply be the result of Aβ accumulation. Alternately, Aβ may unmask an intrinsic susceptibility of DMN circuits. Should DMN vulnerability persist amidst global Aβ deposition, this would support the latter hypothesis. We tested this using long-term, multi-region recordings of single units in mice characterized by widespread Aβ (APP/PS1). We tracked a neuronal population within the retrosplenial cortex (a DMN region) and two monosynaptically connected target populations, one within (anterior cingulate) and the other outside the DMN (primary visual cortex). We also recorded in hippocampus and examined interactions between the in-DMN and out-DMN circuits. Our data revealed progressive dysfunction restricted to the in-DMN circuit. In contrast, communication originating within but targeting an out-DMN population was unaffected by disease. Dysfunction was pronounced in sleep. In a mouse model of amyloid pathology, the authors find deficits in interregional communication specifically in default mode network neural circuits. This suggests these circuits are selectively vulnerable despite widespread plaque burden.