资源环境科技发展态势分析平台

The link between brain amyloid-beta (A beta), metabolism, and dementia symptoms remains a pressing question in Alzheimer's disease. Here, using positron emission tomography ([F-18] florbetapir tracer for A beta and [F-18] FDG tracer for glucose metabolism) with a novel analytical framework, we found that A beta 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 beta aggregation is associated with subsequent cognitive decline. These results were also observed in transgenic A beta 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 beta induces regional metabolic vulnerability, whereas the interaction between local A beta with a vulnerable environment drives the clinical progression of dementia.