title: High striatal amyloid beta-peptide deposition across different autosomal Alzheimer disease mutation types.
abstract: BACKGROUND
  Supported by compelling genetic data regarding early-onset familial Alzheimer disease (AD), the amyloid beta-peptide (Abeta)-centric theory holds that Abeta is involved in the pathogenesis of sporadic AD. Mutations in the amyloid precursor protein (APP), presenilin 1 (PSEN1), and presenilin 2 (PSEN2) genes lead to increased Abeta levels before symptoms arise.
  
  
  OBJECTIVE
  To evaluate the pattern of Pittsburgh Compound B (PiB) retention in subjects with different autosomal dominant mutations associated with familial AD vs that in healthy age-matched control subjects and subjects with probable sporadic AD, to correlate Abeta burden as measured by PiB with available clinical and cognitive data, and to compare the regional brain patterns of PiB retention and fluorodeoxyglucose F 18 (FDG) uptake.
  
  
  METHODS
  Correlation analysis of positron emission tomography (PET) imaging studies.
  
  
  METHODS
  Academic research.
  
  
  METHODS
  Seven PSEN1 mutation carriers and 1 APP mutation carrier underwent PiB and FDG PET imaging. Amyloid beta-peptide burden and FDG uptake were established using standardized uptake values normalized to pons.
  
  
  METHODS
  Primary outcomes were PET results, which were compared with those of a well-characterized cohort of 30 healthy control subjects and 30 subjects with probable sporadic AD.
  
  
  RESULTS
  All mutation carriers had high PiB retention in the striatum, with some also having cortical PiB retention in ventrofrontal and posterior cingulate/precuneus areas. The striatal pattern of PiB retention was similar in the PSEN1 and APP mutation carriers. Neither striatal nor cortical Abeta burden was related to cognitive status.
  
  
  CONCLUSIONS
  Consistent with previous studies, the pattern of Abeta deposition in familial AD differs from that in sporadic AD, with higher striatal and somewhat lower cortical PiB retention in familial AD. The pattern and degree of Abeta deposition were not associated with mutation type nor cognitive status.
authors.affiliation: Department of Nuclear Medicine, Centre for Positron Emission Tomography, Austin Health, Heidelberg, Australia. villemagne@petnm.unimelb.edu.au
authors.forename: Victor L
authors.initials: VL
authors.lastname: Villemagne
authors.forename: Suzuka
authors.initials: S
authors.lastname: Ataka
authors.forename: Toshiki
authors.initials: T
authors.lastname: Mizuno
authors.forename: William S
authors.initials: WS
authors.lastname: Brooks
authors.forename: Yasuhiro
authors.initials: Y
authors.lastname: Wada
authors.forename: Masaki
authors.initials: M
authors.lastname: Kondo
authors.forename: Gareth
authors.initials: G
authors.lastname: Jones
authors.forename: Yasuyoshi
authors.initials: Y
authors.lastname: Watanabe
authors.forename: Rachel
authors.initials: R
authors.lastname: Mulligan
authors.forename: Masanori
authors.initials: M
authors.lastname: Nakagawa
authors.forename: Takami
authors.initials: T
authors.lastname: Miki
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Shimada
authors.forename: Graeme J
authors.initials: GJ
authors.lastname: O'Keefe
authors.forename: Colin L
authors.initials: CL
authors.lastname: Masters
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Mori
authors.forename: Christopher C
authors.initials: CC
authors.lastname: Rowe
mesh_terms: D000328:Adult; D000544:Alzheimer Disease / Q000000981:diagnostic imaging* / Q000235:genetics* / Q000473:pathology; D016229:Amyloid beta-Peptides / Q000235:genetics*; D015331:Cohort Studies; D003342:Corpus Striatum / Q000000981:diagnostic imaging* / Q000473:pathology; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D009154:Mutation / Q000235:genetics*; D010446:Peptide Fragments / Q000235:genetics; D049268:Positron-Emission Tomography
chemical_list: D016229:Amyloid beta-Peptides; D010446:Peptide Fragments