title: A European multicentre PET study of fibrillar amyloid in Alzheimer's disease.
abstract: OBJECTIVE
  Amyloid PET tracers have been developed for in vivo detection of brain fibrillar amyloid deposition in Alzheimer's disease (AD). To serve as an early biomarker in AD the amyloid PET tracers need to be analysed in multicentre clinical studies.
  
  
  METHODS
  In this study 238 [(11)C]Pittsburgh compound-B (PIB) datasets from five different European centres were pooled. Of these 238 datasets, 18 were excluded, leaving [(11)C]PIB datasets from 97 patients with clinically diagnosed AD (mean age 69 ± 8 years), 72 patients with mild cognitive impairment (MCI; mean age 67.5 ± 8 years) and 51 healthy controls (mean age 67.4 ± 6 years) available for analysis. Of the MCI patients, 64 were longitudinally followed for 28 ± 15 months. Most participants (175 out of 220) were also tested for apolipoprotein E (ApoE) genotype.
  
  
  RESULTS
  [(11)C]PIB retention in the neocortical and subcortical brain regions was significantly higher in AD patients than in age-matched controls. Intermediate [(11)C]PIB retention was observed in MCI patients, with a bimodal distribution (64 % MCI PIB-positive and 36 % MCI PIB-negative), which was significantly different the pattern in both the AD patients and controls. Higher [(11)C]PIB retention was observed in MCI ApoE ε4 carriers compared to non-ApoE ε4 carriers (p < 0.005). Of the MCI PIB-positive patients, 67 % had converted to AD at follow-up while none of the MCI PIB-negative patients converted.
  
  
  CONCLUSIONS
  This study demonstrated the robustness of [(11)C]PIB PET as a marker of neocortical fibrillar amyloid deposition in brain when assessed in a multicentre setting. MCI PIB-positive patients showed more severe memory impairment than MCI PIB-negative patients and progressed to AD at an estimated rate of 25 % per year. None of the MCI PIB-negative patients converted to AD, and thus PIB negativity had a 100 % negative predictive value for progression to AD. This supports the notion that PIB-positive scans in MCI patients are an indicator of prodromal AD.
authors.affiliation: Alzheimer Neurobiology Centre,Geriatric Clinic, Karolinska University Hospital Huddinge, Stockholm, Sweden. Agneta.k.Nordberg@ki.se
authors.forename: Agneta
authors.initials: A
authors.lastname: Nordberg
authors.forename: Stephen F
authors.initials: SF
authors.lastname: Carter
authors.forename: Juha
authors.initials: J
authors.lastname: Rinne
authors.forename: Alexander
authors.initials: A
authors.lastname: Drzezga
authors.forename: David J
authors.initials: DJ
authors.lastname: Brooks
authors.forename: Rik
authors.initials: R
authors.lastname: Vandenberghe
authors.forename: Daniela
authors.initials: D
authors.lastname: Perani
authors.forename: Anton
authors.initials: A
authors.lastname: Forsberg
authors.forename: Bengt
authors.initials: B
authors.lastname: Långström
authors.forename: Noora
authors.initials: N
authors.lastname: Scheinin
authors.forename: Mira
authors.initials: M
authors.lastname: Karrasch
authors.forename: Kjell
authors.initials: K
authors.lastname: Någren
authors.forename: Timo
authors.initials: T
authors.lastname: Grimmer
authors.forename: Isabelle
authors.initials: I
authors.lastname: Miederer
authors.forename: Paul
authors.initials: P
authors.lastname: Edison
authors.forename: Aren
authors.initials: A
authors.lastname: Okello
authors.forename: Koen
authors.initials: K
authors.lastname: Van Laere
authors.forename: Natalie
authors.initials: N
authors.lastname: Nelissen
authors.forename: Mathieu
authors.initials: M
authors.lastname: Vandenbulcke
authors.forename: Valentina
authors.initials: V
authors.lastname: Garibotto
authors.forename: Ove
authors.initials: O
authors.lastname: Almkvist
authors.forename: Elke
authors.initials: E
authors.lastname: Kalbe
authors.forename: Rainer
authors.initials: R
authors.lastname: Hinz
authors.forename: Karl
authors.initials: K
authors.lastname: Herholz
mesh_terms: D000368:Aged; D000544:Alzheimer Disease / Q000000981:diagnostic imaging*; D000682:Amyloid / Q000032:analysis*; D000814:Aniline Compounds; D001057:Apolipoproteins E / Q000032:analysis; D001921:Brain / Q000000981:diagnostic imaging; D001923:Brain Chemistry; D016022:Case-Control Studies; D005060:Europe; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D049268:Positron-Emission Tomography; D019275:Radiopharmaceuticals; D013844:Thiazoles
chemical_list: C475519:2-(4'-(methylamino)phenyl)-6-hydroxybenzothiazole; D000682:Amyloid; D000814:Aniline Compounds; D001057:Apolipoproteins E; D019275:Radiopharmaceuticals; D013844:Thiazoles