Relationship between atrophy and β-amyloid deposition in Alzheimer disease

Authors

  • Gaël Chételat PhD,

    Corresponding author
    1. Department of Nuclear Medicine and Center for PET, Austin Health, Heidelberg, Australia
    2. Inserm-EPHE-University of Caen/Basse-Normandie, Unit U923, GIP Cyceron, CHU Côte de Nacre, Caen, France
    • Department of Nuclear Medicine and Centre for PET, Austin Health, 145 Studley Road, Heidelberg, Vic. 3084, Australia
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  • Victor L. Villemagne MD,

    1. Department of Nuclear Medicine and Center for PET, Austin Health, Heidelberg, Australia
    2. Mental Health Research Institute, University of Melbourne, Melbourne, Australia
    3. Department of Medicine, Austin Health, University of Melbourne, Heidelberg, Australia
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  • Pierrick Bourgeat PhD,

    1. CSIRO Preventative Health National Research Flagship ICTC, Australian e-Health Research Centre, BioMedIA, Royal Brisbane and Women's Hospital, Herston, Australia
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  • Kerryn E. Pike DPsych,

    1. Department of Nuclear Medicine and Center for PET, Austin Health, Heidelberg, Australia
    2. Mental Health Research Institute, University of Melbourne, Melbourne, Australia
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  • Gareth Jones BSc,

    1. Department of Nuclear Medicine and Center for PET, Austin Health, Heidelberg, Australia
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  • David Ames MD,

    1. National Ageing Research Institute, Melbourne, Australia
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  • Kathryn A. Ellis PhD,

    1. Academic Unit for Psychiatry of Old Age, Department of Psychiatry, University of Melbourne, St. Vincent's Aged Psychiatry Service, St George's Hospital, Melbourne, Australia
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  • Cassandra Szoeke PhD,

    1. CSIRO Preventative Health National Research Flagship ICTC, Australian e-Health Research Centre, BioMedIA, Royal Brisbane and Women's Hospital, Herston, Australia
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  • Ralph N. Martins PhD,

    1. Centre of Excellence for Alzheimer's Disease Research & Care, School of Exercise, Biomedical, and Health Sciences, Edith Cowan University, Joondalup, Australia
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  • Graeme J. O'Keefe PhD,

    1. Department of Nuclear Medicine and Center for PET, Austin Health, Heidelberg, Australia
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  • Olivier Salvado PhD,

    1. CSIRO Preventative Health National Research Flagship ICTC, Australian e-Health Research Centre, BioMedIA, Royal Brisbane and Women's Hospital, Herston, Australia
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  • Colin L. Masters MD,

    1. Mental Health Research Institute, University of Melbourne, Melbourne, Australia
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  • Christopher C. Rowe MD

    1. Department of Nuclear Medicine and Center for PET, Austin Health, Heidelberg, Australia
    2. Department of Medicine, Austin Health, University of Melbourne, Heidelberg, Australia
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Abstract

Objective

Elucidating the role of aggregated β-amyloid in relation to gray matter atrophy is crucial to the understanding of the pathological mechanisms of Alzheimer disease and for the development of therapeutic trials. The present study aims to assess this relationship.

Methods

Brain magnetic resonance imaging and [11C]Pittsburgh compound B (PiB)-positron emission tomography scans were obtained from 94 healthy elderly subjects (49 with subjective cognitive impairment), 34 patients with mild cognitive impairment, and 35 patients with Alzheimer disease. The correlations between global and regional neocortical PiB retention and atrophy were analyzed in each clinical group.

Results

Global and regional atrophy were strongly related to β-amyloid load in participants with subjective cognitive impairment but not in patients with mild cognitive impairment or Alzheimer disease. Global neocortical β-amyloid deposition correlated to atrophy in a large brain network including the hippocampus, medial frontal and parietal areas, and lateral temporoparietal cortex, whereas regional β-amyloid load was related to local atrophy in the areas of highest β-amyloid load only, that is, medial orbitofrontal and anterior and posterior cingulate/precuneus areas.

Interpretation

There is a strong relationship between β-amyloid deposition and atrophy very early in the disease process. As the disease progresses to mild cognitive impairment and Alzheimer disease clinical stages, pathological events other than, and probably downstream from, aggregated β-amyloid deposition might be responsible for the ongoing atrophic process. These findings suggest that antiamyloid therapy should be administered very early in the disease evolution to minimize synaptic and neuronal loss. ANN NEUROL 2010;67:317–324

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