Aβ-induced vulnerability propagates via the brain’s default mode network
T. Pascoal, S. Mathotaarachchi, M. Kang, Sara Mohaddes, M. Shin, A. Park, Maxime J Parent, A. Benedet, M. Chamoun, Joseph Therriault, Heungsun Hwang, A. Cuello, B. Mišić, J. Soucy, J. Aston, S. Gauthier, Pedro Rosa‐neto
Nature Communications June 4, 2019 DOI: 10.1038/s41467-019-10217-w (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Observational study with transgenic animal model Peer reviewed |
|---|---|
| Population | Humans and transgenic Aβ rats |
| Topics | Default mode network |
| Key findings | Aβ aggregation in the default mode network leads to hypometabolism in distant but functionally connected brain regions, and the interaction of this hypometabolism with overlapping Aβ aggregation is associated with subsequent cognitive decline. |
Abstract
The link between brain amyloid-β (Aβ), metabolism, and dementia symptoms remains a pressing question in Alzheimer’s disease. Here, using positron emission tomography ([18F]florbetapir tracer for Aβ and [18F]FDG tracer for glucose metabolism) with a novel analytical framework, we found that Aβ 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 Aβ aggregation is associated with subsequent cognitive decline. These results were also observed in transgenic Aβ 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 Aβ induces regional metabolic vulnerability, whereas the interaction between local Aβ with a vulnerable environment drives the clinical progression of dementia. Amyloid-β (Aβ) deposition occurs in Alzheimer's disease but its relation to disease features such as local brain hypometabolism or cognitive decline is unclear. Here, the authors show that Aβ aggregation in the brain’s default mode network leads to hypometabolism in distant but functionally connected areas.
Comparable studies
Other preclinical and animal studies on default mode network, most cited first.
| Study | Year | Design | Participants |
|---|---|---|---|
| Rat brains also have a default mode network Rats | 2012 | Observational study | |
| Large-scale topology and the default mode network in the mouse connectome Mouse brain | 2014 | Observational study | |
| Hippocampal Sharp-Wave Ripples Influence Selective Activation of the Default Mode Network Anesthetized monkeys | 2016 | Observational study | |
| Psilocybin-induced default mode network hypoconnectivity is blunted in alcohol-dependent rats Healthy rats and a rat model of alcohol relapse | 2023 | Randomized, placebo-controlled crossover pharmaco-fMRI study | |
| Altered functional connectivity within the default mode network in two animal models with opposing episodic memories Rats (control, LPS-challenged, and footshock-exposed groups) | 2018 | Animal model study |