Aβ-induced vulnerability propagates via the brain’s default mode network
Nature Communications June 4, 2019 T. Pascoal, S. Mathotaarachchi, M. Kang et al.
Amyloid-β (Aβ) aggregation in the brain's default mode network leads to reduced glucose metabolism in distant but functionally connected brain regions. The interaction between this hypometabolism and overlapping Aβ aggregation is associated with subsequent cognitive decline. These results were also observed in transgenic Aβ rats that do not form neurofibrillary tangles, supporting these findings as an independent mechanism of cognitive deterioration. The findings suggest a model where distant Aβ induces regional metabolic vulnerability, while the interaction between local Aβ with a vulnerable environment drives the clinical progression of dementia.