title: Microglial activation and amyloid deposition in mild cognitive impairment: a PET study.
abstract: BACKGROUND
  Activated microglia may play a role in the pathogenesis of Alzheimer disease (AD) as they cluster around beta-amyloid (Abeta) plaques. They are, therefore, a potential therapeutic target in both AD and its prodrome amnestic mild cognitive impairment (MCI).
  
  
  OBJECTIVE
  To characterize in vivo with (11)C-(R)-PK11195 and (11)C-PIB PET the distribution of microglial activation and amyloid deposition in patients with amnestic MCI.
  
  
  METHODS
  Fourteen subjects with MCI had (11)C-(R)-PK11195 and (11)C-PIB PET with psychometric tests.
  
  
  RESULTS
  Seven out of 14 (50%) patients with MCI had increased cortical (11)C-PIB retention (p < 0.001) while 5 out of 13 (38%) subjects with MCI showed increased (11)C-(R)-PK11195 uptake. The MCI subgroup with increased (11)C-PIB retention also showed increased cortical (11)C-(R)-PK11195 binding (p < 0.036) though this increase only remained significant in frontal cortex after a correction for multiple comparisons. There was no correlation between regional levels of (11)C-(R)-PK11195 and (11)C-PIB binding in individual patients with MCI: only three of the five MCI cases with increased (11)C-(R)-PK11195 binding had increased levels of (11)C-PIB retention.
  
  
  CONCLUSIONS
  Our findings indicate that, while amyloid deposition and microglial activation can be detected in vivo in around 50% of patients with mild cognitive impairment (MCI), these pathologies can occur independently. The detection of microglial activation in patients with MCI suggests that anti-inflammatory therapies may be relevant to the prevention of AD.
authors.affiliation: Division of Neuroscience and Mental Health, Faculty of Medicine, Imperial College London, London, UK. aren.okello@imperial.ac.uk
authors.forename: A
authors.initials: A
authors.lastname: Okello
authors.forename: P
authors.initials: P
authors.lastname: Edison
authors.forename: H A
authors.initials: HA
authors.lastname: Archer
authors.forename: F E
authors.initials: FE
authors.lastname: Turkheimer
authors.forename: J
authors.initials: J
authors.lastname: Kennedy
authors.forename: R
authors.initials: R
authors.lastname: Bullock
authors.forename: Z
authors.initials: Z
authors.lastname: Walker
authors.forename: A
authors.initials: A
authors.lastname: Kennedy
authors.forename: N
authors.initials: N
authors.lastname: Fox
authors.forename: M
authors.initials: M
authors.lastname: Rossor
authors.forename: D J
authors.initials: DJ
authors.lastname: Brooks
mesh_terms: D000368:Aged; D000544:Alzheimer Disease / Q000150:complications; D016229:Amyloid beta-Peptides / Q000378:metabolism*; D000814:Aniline Compounds; D052160:Benzothiazoles / Q000378:metabolism; D001931:Brain Mapping; D002250:Carbon Radioisotopes / Q000378:metabolism; D003072:Cognition Disorders / Q000175:diagnosis / Q000000981:diagnostic imaging* / Q000209:etiology / Q000473:pathology*; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D007546:Isoquinolines / Q000378:metabolism; D008279:Magnetic Resonance Imaging; D008297:Male; D017628:Microglia / Q000000981:diagnostic imaging* / Q000378:metabolism / Q000473:pathology; D008875:Middle Aged; D009483:Neuropsychological Tests; D049268:Positron-Emission Tomography; D013844:Thiazoles
chemical_list: C475519:2-(4'-(methylamino)phenyl)-6-hydroxybenzothiazole; D016229:Amyloid beta-Peptides; D000814:Aniline Compounds; D052160:Benzothiazoles; D002250:Carbon Radioisotopes; D007546:Isoquinolines; D013844:Thiazoles; C037850:PK 11195