In-vivo measurement of activated microglia in dementia.
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.
Cagnin
A
A
MRC Cyclotron Unit, Imperial College, Faculty of Medicine, Division of Neuroscience and Psychological Medicince, Hammersmith Hospital, London, UK.
Brooks
D J
DJ
Kennedy
A M
AM
Gunn
R N
RN
Myers
R
R
Turkheimer
F E
FE
Jones
T
T
Banati
R B
RB
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
D002250:Carbon Radioisotopes; D007546:Isoquinolines; D011963:Receptors, GABA-A; C037850:PK 11195