title: Relationship between atrophy and beta-amyloid deposition in Alzheimer disease.
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.
  
  
  METHODS
  Brain magnetic resonance imaging and [(11)C]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 beta-amyloid load in participants with subjective cognitive impairment but not in patients with mild cognitive impairment or Alzheimer disease. Global neocortical beta-amyloid deposition correlated to atrophy in a large brain network including the hippocampus, medial frontal and parietal areas, and lateral temporoparietal cortex, whereas regional beta-amyloid load was related to local atrophy in the areas of highest beta-amyloid load only, that is, medial orbitofrontal and anterior and posterior cingulate/precuneus areas.
  
  
  CONCLUSIONS
  There is a strong relationship between beta-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 beta-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.
authors.affiliation: Department of Nuclear Medicine and Center for PET, Austin Health, 145 Studley Road, Heidelberg, Victoria 3084, Australia. chetelate@cyceron.fr
authors.forename: Gaël
authors.initials: G
authors.lastname: Chételat
authors.forename: Victor L
authors.initials: VL
authors.lastname: Villemagne
authors.forename: Pierrick
authors.initials: P
authors.lastname: Bourgeat
authors.forename: Kerryn E
authors.initials: KE
authors.lastname: Pike
authors.forename: Gareth
authors.initials: G
authors.lastname: Jones
authors.forename: David
authors.initials: D
authors.lastname: Ames
authors.forename: Kathryn A
authors.initials: KA
authors.lastname: Ellis
authors.forename: Cassandra
authors.initials: C
authors.lastname: Szoeke
authors.forename: Ralph N
authors.initials: RN
authors.lastname: Martins
authors.forename: Graeme J
authors.initials: GJ
authors.lastname: O'Keefe
authors.forename: Olivier
authors.initials: O
authors.lastname: Salvado
authors.forename: Colin L
authors.initials: CL
authors.lastname: Masters
authors.forename: Christopher C
authors.initials: CC
authors.lastname: Rowe
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000544:Alzheimer Disease / Q000000981:diagnostic imaging / Q000378:metabolism / Q000473:pathology*; D016229:Amyloid beta-Peptides / Q000032:analysis* / Q000378:metabolism; D000814:Aniline Compounds; D001284:Atrophy / Q000000981:diagnostic imaging / Q000378:metabolism / Q000473:pathology*; D052160:Benzothiazoles; D015415:Biomarkers / Q000032:analysis / Q000378:metabolism; D001921:Brain / Q000000981:diagnostic imaging / Q000378:metabolism / Q000473:pathology*; D003072:Cognition Disorders / Q000000981:diagnostic imaging / Q000378:metabolism / Q000473:pathology; D018450:Disease Progression; D005260:Female; D006801:Humans; D008279:Magnetic Resonance Imaging; D008297:Male; D058225:Plaque, Amyloid / Q000000981:diagnostic imaging / Q000378:metabolism / Q000473:pathology*; D049268:Positron-Emission Tomography; D011237:Predictive Value of Tests; D011379:Prognosis; D012720:Severity of Illness Index; D013844:Thiazoles
chemical_list: C475519:2-(4'-(methylamino)phenyl)-6-hydroxybenzothiazole; D016229:Amyloid beta-Peptides; D000814:Aniline Compounds; D052160:Benzothiazoles; D015415:Biomarkers; D013844:Thiazoles