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

Author

Listed:
  • Tharick A. Pascoal

    (The McGill University Research Centre for Studies in Aging
    Montreal Neurological Institute)

  • Sulantha Mathotaarachchi

    (The McGill University Research Centre for Studies in Aging)

  • Min Su Kang

    (The McGill University Research Centre for Studies in Aging
    Montreal Neurological Institute)

  • Sara Mohaddes

    (The McGill University Research Centre for Studies in Aging)

  • Monica Shin

    (The McGill University Research Centre for Studies in Aging)

  • Ah Yeon Park

    (University of Cambridge)

  • Maxime J. Parent

    (The McGill University Research Centre for Studies in Aging
    Montreal Neurological Institute)

  • Andrea L. Benedet

    (The McGill University Research Centre for Studies in Aging)

  • Mira Chamoun

    (The McGill University Research Centre for Studies in Aging)

  • Joseph Therriault

    (The McGill University Research Centre for Studies in Aging)

  • Heungsun Hwang

    (McGill University)

  • A. Claudio Cuello

    (McGill University
    The McGill University Research Centre for Studies in Aging)

  • Bratislav Misic

    (Montreal Neurological Institute)

  • Jean-Paul Soucy

    (Montreal Neurological Institute)

  • John A. D. Aston

    (University of Cambridge)

  • Serge Gauthier

    (The McGill University Research Centre for Studies in Aging)

  • Pedro Rosa-Neto

    (The McGill University Research Centre for Studies in Aging
    Montreal Neurological Institute
    McGill University
    The McGill University Research Centre for Studies in Aging)

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.

Suggested Citation

  • Tharick A. Pascoal & Sulantha Mathotaarachchi & Min Su Kang & Sara Mohaddes & Monica Shin & Ah Yeon Park & Maxime J. Parent & Andrea L. Benedet & Mira Chamoun & Joseph Therriault & Heungsun Hwang & A., 2019. "Aβ-induced vulnerability propagates via the brain’s default mode network," Nature Communications, Nature, vol. 10(1), pages 1-13, December.
    • Handle: RePEc:nat:natcom:v:10:y:2019:i:1:d:10.1038_s41467-019-10217-w
    DOI: 10.1038/s41467-019-10217-w
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