A?-induced vulnerability propagates via the brain's default mode network.

ABSTRACT: The link between brain amyloid-? (A?), metabolism, and dementia symptoms remains a pressing question in Alzheimer's disease. Here, using positron emission tomography ([¹⁸F]florbetapir tracer for A? and [¹⁸F]FDG tracer for glucose metabolism) with a novel analytical framework, we found that A? aggregation within the brain's default mode network leads to regional hypometabolism in distant but functionally connected brain regions. Moreover, we found that an interaction between this hypometabolism with overlapping A? aggregation is associated with subsequent cognitive decline. These results were also observed in transgenic A? rats that do not form neurofibrillary tangles, which support these findings as an independent mechanism of cognitive deterioration. These results suggest a model in which distant A? induces regional metabolic vulnerability, whereas the interaction between local A? with a vulnerable environment drives the clinical progression of dementia.

SUBMITTER: Pascoal TA 

PROVIDER: S-EPMC6547716 | biostudies-literature | 2019 Jun

REPOSITORIES: biostudies-literature