title: Microglia, amyloid, and cognition in Alzheimer's disease: An [11C](R)PK11195-PET and [11C]PIB-PET study.
abstract: [11C](R)PK11195-PET is a marker of activated microglia while [11C]PIB-PET detects raised amyloid load. Here we studied in vivo the distributions of amyloid load and microglial activation in Alzheimer's disease (AD) and their relationship with cognitive status. Thirteen AD subjects had [11C](R)PK11195-PET and [11C]PIB-PET scans. Ten healthy controls had [11C](R)PK11195-PET and 14 controls had [11C]PIB-PET scans. Region-of-interest analysis of [11C](R)PK11195-PET detected significant 20-35% increases in microglial activation in frontal, temporal, parietal, occipital and cingulate cortices (p<0.05) of the AD subjects. [11C]PIB-PET revealed significant two-fold increases in amyloid load in these same cortical areas (p<0.0001) and SPM (statistical parametric mapping) analysis confirmed the localisation of these increases to association areas. MMSE scores in AD subjects correlated with levels of cortical microglial activation but not with amyloid load. The inverse correlation between MMSE and microglial activation is compatible with a role of microglia in neuronal damage.
authors.affiliation: MRC Clinical Sciences Centre, Cyclotron Building Hammersmith Hospital, Imperial College London, UK. paul.edison@imperial.ac.uk
authors.forename: Paul
authors.initials: P
authors.lastname: Edison
authors.forename: Hilary A
authors.initials: HA
authors.lastname: Archer
authors.forename: Alexander
authors.initials: A
authors.lastname: Gerhard
authors.forename: Rainer
authors.initials: R
authors.lastname: Hinz
authors.forename: Nicola
authors.initials: N
authors.lastname: Pavese
authors.forename: Federico E
authors.initials: FE
authors.lastname: Turkheimer
authors.forename: Alexander
authors.initials: A
authors.lastname: Hammers
authors.forename: Yen Fong
authors.initials: YF
authors.lastname: Tai
authors.forename: Nick
authors.initials: N
authors.lastname: Fox
authors.forename: Angus
authors.initials: A
authors.lastname: Kennedy
authors.forename: Martin
authors.initials: M
authors.lastname: Rossor
authors.forename: David J
authors.initials: DJ
authors.lastname: Brooks
mesh_terms: D000368:Aged; D000544:Alzheimer Disease / Q000000981:diagnostic imaging* / Q000503:physiopathology / Q000523:psychology; D000682:Amyloid / Q000032:analysis*; D000814:Aniline Compounds; D002250:Carbon Radioisotopes; D002540:Cerebral Cortex / Q000737:chemistry / Q000000981:diagnostic imaging* / Q000503:physiopathology; D016000:Cluster Analysis; D003071:Cognition; D005260:Female; D006801:Humans; D007546:Isoquinolines; D008279:Magnetic Resonance Imaging; D008297:Male; D017628:Microglia / Q000502:physiology*; D008875:Middle Aged; D049268:Positron-Emission Tomography; D013844:Thiazoles
chemical_list: C475519:2-(4'-(methylamino)phenyl)-6-hydroxybenzothiazole; D000682:Amyloid; D000814:Aniline Compounds; D002250:Carbon Radioisotopes; D007546:Isoquinolines; D013844:Thiazoles; C037850:PK 11195