Microglial activation and amyloid deposition in mild cognitive impairment: a PET study.
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.
Okello
A
A
Division of Neuroscience and Mental Health, Faculty of Medicine, Imperial College London, London, UK. aren.okello@imperial.ac.uk
Edison
P
P
Archer
H A
HA
Turkheimer
F E
FE
Kennedy
J
J
Bullock
R
R
Walker
Z
Z
Kennedy
A
A
Fox
N
N
Rossor
M
M
Brooks
D J
DJ
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
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