title: In-vivo measurement of activated microglia in dementia.
abstract: BACKGROUND
  Activated microglia have a key role in the brain's immune response to neuronal degeneration. The transition of microglia from the normal resting state to the activated state is associated with an increased expression of receptors known as peripheral benzodiazepine binding sites, which are abundant on cells of mononuclear phagocyte lineage. We used brain imaging to study expression of these sites in healthy individuals and patients with Alzheimer's disease.
  
  
  METHODS
  We studied 15 normal individuals (age 32-80 years), eight patients with Alzheimer's disease, and one patient with minimal cognitive impairment. Quantitative in-vivo measurements of glial activation were obtained with positron emission tomography (PET) and carbon-11-labelled (R)-PK11195, a specific ligand for the peripheral benzodiazepine binding site.
  
  
  RESULTS
  In normal individuals, regional [11C](R)-PK11195 binding did not significantly change with age, except in the thalamus, where an age-dependent increase was found. By contrast, patients with Alzheimer's disease showed significantly increased regional [11C](R)-PK11195 binding in the entorhinal, temporoparietal, and cingulate cortex.
  
  
  CONCLUSIONS
  In-vivo detection of increased [11C](R)-PK11195 binding in Alzheimer-type dementia, including mild and early forms, suggests that microglial activation is an early event in the pathogenesis of the disease.
authors.affiliation: MRC Cyclotron Unit, Imperial College, Faculty of Medicine, Division of Neuroscience and Psychological Medicince, Hammersmith Hospital, London, UK.
authors.forename: A
authors.initials: A
authors.lastname: Cagnin
authors.forename: D J
authors.initials: DJ
authors.lastname: Brooks
authors.forename: A M
authors.initials: AM
authors.lastname: Kennedy
authors.forename: R N
authors.initials: RN
authors.lastname: Gunn
authors.forename: R
authors.initials: R
authors.lastname: Myers
authors.forename: F E
authors.initials: FE
authors.lastname: Turkheimer
authors.forename: T
authors.initials: T
authors.lastname: Jones
authors.forename: R B
authors.initials: RB
authors.lastname: Banati
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000544:Alzheimer Disease / Q000000981:diagnostic imaging* / Q000209:etiology / Q000473:pathology; D001284:Atrophy; D001921:Brain / Q000000981:diagnostic imaging* / Q000378:metabolism / Q000473:pathology; D002250:Carbon Radioisotopes; D016022:Case-Control Studies; D005260:Female; D006801:Humans; D007249:Inflammation / Q000473:pathology; D007546:Isoquinolines; D008279:Magnetic Resonance Imaging; D008297:Male; D017628:Microglia / Q000473:pathology*; D008875:Middle Aged; D011963:Receptors, GABA-A / Q000378:metabolism; D014055:Tomography, Emission-Computed
chemical_list: D002250:Carbon Radioisotopes; D007546:Isoquinolines; D011963:Receptors, GABA-A; C037850:PK 11195