title: In vivo changes in microglial activation and amyloid deposits in brain regions with hypometabolism in Alzheimer's disease.
abstract: OBJECTIVE
  Amyloid β protein (Aβ) is known as a pathological substance in Alzheimer's disease (AD) and is assumed to coexist with a degree of activated microglia in the brain. However, it remains unclear whether these two events occur in parallel with characteristic hypometabolism in AD in vivo. The purpose of the present study was to clarify the in vivo relationship between Aβ accumulation and neuroinflammation in those specific brain regions in early AD.
  
  
  METHODS
  Eleven nootropic drug-naïve AD patients underwent a series of positron emission tomography (PET) measurements with [(11)C](R)PK11195, [(11)C]PIB and [(18)F]FDG and a battery of cognitive tests within the same day. The binding potentials (BPs) of [(11)C](R)PK11195 were directly compared with those of [(11)C]PIB in the brain regions with reduced glucose metabolism.
  
  
  RESULTS
  BPs of [(11)C](R)PK11195 and [(11)C]PIB were significantly higher in the parietotemporal regions of AD patients than in ten healthy controls. In AD patients, there was a negative correlation between dementia score and [(11)C](R)PK11195 BPs, but not [(11)C]PIB, in the limbic, precuneus and prefrontal regions. Direct comparisons showed a significant negative correlation between [(11)C](R)PK11195 and [(11)C]PIB BPs in the posterior cingulate cortex (PCC) (p < 0.05, corrected) that manifested the most severe reduction in [(18)F]FDG uptake.
  
  
  CONCLUSIONS
  A lack of coupling between microglial activation and amyloid deposits may indicate that Aβ accumulation shown by [(11)C]PIB is not always the primary cause of microglial activation, but rather the negative correlation present in the PCC suggests that microglia can show higher activation during the production of Aβ in early AD.
authors.affiliation: Department of Psychiatry and Neurology, Hamamatsu University School of Medicine, Hamamatsu, Japan.
authors.forename: Masamichi
authors.initials: M
authors.lastname: Yokokura
authors.forename: Norio
authors.initials: N
authors.lastname: Mori
authors.forename: Shunsuke
authors.initials: S
authors.lastname: Yagi
authors.forename: Etsuji
authors.initials: E
authors.lastname: Yoshikawa
authors.forename: Mitsuru
authors.initials: M
authors.lastname: Kikuchi
authors.forename: Yujiro
authors.initials: Y
authors.lastname: Yoshihara
authors.forename: Tomoyasu
authors.initials: T
authors.lastname: Wakuda
authors.forename: Genichi
authors.initials: G
authors.lastname: Sugihara
authors.forename: Kiyokazu
authors.initials: K
authors.lastname: Takebayashi
authors.forename: Shiro
authors.initials: S
authors.lastname: Suda
authors.forename: Yasuhide
authors.initials: Y
authors.lastname: Iwata
authors.forename: Takatoshi
authors.initials: T
authors.lastname: Ueki
authors.forename: Kenji J
authors.initials: KJ
authors.lastname: Tsuchiya
authors.forename: Katsuaki
authors.initials: K
authors.lastname: Suzuki
authors.forename: Kazuhiko
authors.initials: K
authors.lastname: Nakamura
authors.forename: Yasuomi
authors.initials: Y
authors.lastname: Ouchi
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000544:Alzheimer Disease / Q000000981:diagnostic imaging / Q000378:metabolism* / Q000473:pathology*; D016229:Amyloid beta-Peptides / Q000378:metabolism*; D001921:Brain / Q000000981:diagnostic imaging / Q000378:metabolism* / Q000473:pathology*; D016022:Case-Control Studies; D005260:Female; D005947:Glucose / Q000378:metabolism; D006801:Humans; D008297:Male; D017628:Microglia / Q000378:metabolism*; D008875:Middle Aged; D009474:Neurons / Q000473:pathology; D049268:Positron-Emission Tomography; D011849:Radioactive Tracers
chemical_list: D016229:Amyloid beta-Peptides; D011849:Radioactive Tracers; D005947:Glucose