Microglia, amyloid, and cognition in Alzheimer's disease: An [11C](R)PK11195-PET and [11C]PIB-PET study.
[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.
Edison
Paul
P
MRC Clinical Sciences Centre, Cyclotron Building Hammersmith Hospital, Imperial College London, UK. paul.edison@imperial.ac.uk
Archer
Hilary A
HA
Gerhard
Alexander
A
Hinz
Rainer
R
Pavese
Nicola
N
Turkheimer
Federico E
FE
Hammers
Alexander
A
Tai
Yen Fong
YF
Fox
Nick
N
Kennedy
Angus
A
Rossor
Martin
M
Brooks
David J
DJ
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
C475519:2-(4'-(methylamino)phenyl)-6-hydroxybenzothiazole; D000682:Amyloid; D000814:Aniline Compounds; D002250:Carbon Radioisotopes; D007546:Isoquinolines; D013844:Thiazoles; C037850:PK 11195