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

The link between brain amyloid-β (Aβ), metabolism, and dementia symptoms remains a pressing question in Alzheimer's disease. Here, using positron emission tomography ([ F]florbetapir tracer for Aβ and [ F]FDG tracer for glucose metabolism) with a novel analytical framework, we found that Aβ agg...

Full description

Saved in:

Bibliographic Details
Published in:	Nature communications 2019-06, Vol.10 (1), p.2353-2353, Article 2353
Main Authors:	Pascoal, Tharick A, Mathotaarachchi, Sulantha, Kang, Min Su, Mohaddes, Sara, Shin, Monica, Park, Ah Yeon, Parent, Maxime J, Benedet, Andrea L, Chamoun, Mira, Therriault, Joseph, Hwang, Heungsun, Cuello, A Claudio, Misic, Bratislav, Soucy, Jean-Paul, Aston, John A D, Gauthier, Serge, Rosa-Neto, Pedro
Format:	Article
Language:	eng
Subjects:	Agglomeration Alzheimer Disease - diagnostic imaging Alzheimer Disease - metabolism Amyloid beta-Peptides - metabolism Aniline Compounds Animals Animals, Genetically Modified Brain Brain - diagnostic imaging Brain - metabolism Cognitive ability Cognitive Dysfunction - diagnostic imaging Cognitive Dysfunction - metabolism Dementia Dementia disorders Ethylene Glycols Fluorodeoxyglucose F18 Glucose metabolism Humans Hypometabolism Magnetic Resonance Imaging Metabolism Neural Pathways - diagnostic imaging Neural Pathways - metabolism Neurofibrillary tangles Neurofibrillary Tangles - metabolism Positron emission Positron emission tomography Radiopharmaceuticals Rats Signs and symptoms
Online Access:	Get full text
Tags:	Add Tag No Tags, Be the first to tag this record!

Description
Summary:	The link between brain amyloid-β (Aβ), metabolism, and dementia symptoms remains a pressing question in Alzheimer's disease. Here, using positron emission tomography ([ F]florbetapir tracer for Aβ and [ F]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.
ISSN:	2041-1723 2041-1723