Relationship between atrophy and beta-amyloid deposition in Alzheimer disease

Chetelat, Gael, Villemagne, Victor L., Bourgeat, Pierrick, Pike, Kerryn E., Jones, Gareth, Ames, David, Ellis, Kathryn A., Szoeke, Cassandra, Martins, Ralph N., O'Keefe, Graeme J., Salvado, Olivier, Masters, Colin L., Rowe, Christopher C. and Australian Imaging Biomarkers and Lifestyle Research Group (2010) Relationship between atrophy and beta-amyloid deposition in Alzheimer disease. Annals of Neurology, 67 3: 317-324. doi:10.1002/ana.21955


Author Chetelat, Gael
Villemagne, Victor L.
Bourgeat, Pierrick
Pike, Kerryn E.
Jones, Gareth
Ames, David
Ellis, Kathryn A.
Szoeke, Cassandra
Martins, Ralph N.
O'Keefe, Graeme J.
Salvado, Olivier
Masters, Colin L.
Rowe, Christopher C.
Australian Imaging Biomarkers and Lifestyle Research Group
Title Relationship between atrophy and beta-amyloid deposition in Alzheimer disease
Formatted title
Relationship between atrophy and β-amyloid deposition in Alzheimer disease
Journal name Annals of Neurology   Check publisher's open access policy
ISSN 0364-5134
1531-8249
Publication date 2010-03-01
Year available 2009
Sub-type Article (original research)
DOI 10.1002/ana.21955
Open Access Status Not yet assessed
Volume 67
Issue 3
Start page 317
End page 324
Total pages 8
Place of publication Hoboken, NJ, United States
Publisher John Wiley & Sons
Language eng
Abstract Objective: Elucidating the role of aggregated beta-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.
Formatted 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.
Keyword Clinical Neurology
Neurosciences
Neurosciences & Neurology
CLINICAL NEUROLOGY
NEUROSCIENCES
Q-Index Code C1
Q-Index Status Provisional Code
Institutional Status Non-UQ
Additional Notes Article first published online: 23 DEC 2009

 
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