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Nat Commun. 2019 Jun 4;10(1):2353. doi: 10.1038/s41467-019-10217-w.

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

Author information

1
Translational Neuroimaging Laboratory, The McGill University Research Centre for Studies in Aging, H4H 1R3, Montreal, Canada.
2
Montreal Neurological Institute, H3A 2B4, Montreal, Canada.
3
Statistical Laboratory, University of Cambridge, CB3 0WB, Cambridge, UK.
4
Department of Psychology, McGill University, Montreal, Canada.
5
Department of Pharmacology and Therapeutics, McGill University, H3A 2T5, Montreal, Canada.
6
Alzheimer's Disease Research Unit, The McGill University Research Centre for Studies in Aging, H4H 1R3, Montreal, Canada.
7
Translational Neuroimaging Laboratory, The McGill University Research Centre for Studies in Aging, H4H 1R3, Montreal, Canada. pedro.rosa@mcgill.ca.
8
Montreal Neurological Institute, H3A 2B4, Montreal, Canada. pedro.rosa@mcgill.ca.
9
Department of Pharmacology and Therapeutics, McGill University, H3A 2T5, Montreal, Canada. pedro.rosa@mcgill.ca.
10
Alzheimer's Disease Research Unit, The McGill University Research Centre for Studies in Aging, H4H 1R3, Montreal, Canada. pedro.rosa@mcgill.ca.

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.

PMID:
31164641
PMCID:
PMC6547716
DOI:
10.1038/s41467-019-10217-w
[Indexed for MEDLINE]
Free PMC Article

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