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© 2009 American Academy of Neurology Microglial activation and amyloid deposition in mild cognitive impairmentA PET studyFrom the Division of Neuroscience and Mental Health (A.O., P.E., F.E.T., A.K., D.J.B.), Faculty of Medicine, Imperial College London; Dementia Research Centre, Department of Neurodegenerative Disease, Institute of Neurology (H.A.A., J.K., N.F., M.R.), and Department of Mental Health Sciences (Z.W.), University College London; Kingshill Research Centre (R.B.), Victoria Hospital, Swindon; and Hammersmith Imanet (D.J.B.), GE Healthcare, London, UK. Address correspondence and reprint requests to Dr. Aren Okello, Cyclotron Building, Hammersmith Hospital, Du Cane Road, London, W12 0NN, UK aren.okello{at}imperial.ac.uk Background: Activated microglia may play a role in the pathogenesis of Alzheimer disease (AD) as they cluster around beta-amyloid (Aβ) 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 11C-(R)-PK11195 and 11C-PIB PET the distribution of microglial activation and amyloid deposition in patients with amnestic MCI. Methods: Fourteen subjects with MCI had 11C-(R)-PK11195 and 11C-PIB PET with psychometric tests. Results: Seven out of 14 (50%) patients with MCI had increased cortical 11C-PIB retention (p < 0.001) while 5 out of 13 (38%) subjects with MCI showed increased 11C-(R)-PK11195 uptake. The MCI subgroup with increased 11C-PIB retention also showed increased cortical 11C-(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 11C-(R)-PK11195 and 11C-PIB binding in individual patients with MCI: only three of the five MCI cases with increased 11C-(R)-PK11195 binding had increased levels of 11C-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.
Abbreviations: Aβ = beta-amyloid; AD = Alzheimer disease; BP = binding potential; MCI = mild cognitive impairment; MMSE = Mini-Mental State Examination; PBBS = peripheral benzodiazepine binding site; ROI = region of interest; SD = standard deviation; SRTM = simplified reference tissue model.
Supplemental data at www.neurology.org Disclosure: This work was conducted in collaboration with Imanet, GE Healthcare. The Dementia Research Centre is an Alzheimer's Research Trust Coordinating Centre. UCLH/UCL received a proportion of funding from the Department of Health's NIHR Biomedical Research Centres funding scheme. A. Okello is an Alzheimer's Research Trust research associate; P. Edison is a Medical Research Council clinical research fellow; H. Archer received funding from the Alzheimer's Research Trust; J. Kennedy is supported by funding from the Alzheimer's Research Trust; Z. Walker has received consultancy fees from GE Healthcare; N. Fox is a Medical Research Council senior clinical fellow; David Brooks is Head of Neurology, Medical Diagnostics, GE Healthcare. Received July 1, 2008. Accepted in final form September 25, 2008. This article has been cited by other articles:
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