Volume 11, Issue 6 p. 608-621.e7
Featured Article

Influence of microglial activation on neuronal function in Alzheimer's and Parkinson's disease dementia

Zhen Fan

Zhen Fan

Neurology Imaging Unit, Department of Medicine, Imperial College London, Hammersmith Hospital, London, UK

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Yahyah Aman

Yahyah Aman

Neurology Imaging Unit, Department of Medicine, Imperial College London, Hammersmith Hospital, London, UK

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Imtiaz Ahmed

Imtiaz Ahmed

Neurology Imaging Unit, Department of Medicine, Imperial College London, Hammersmith Hospital, London, UK

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Gaël Chetelat

Gaël Chetelat

Inserm-EPHE-University of Caen/Basse-Normandie, Caen, France

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Brigitte Landeau

Brigitte Landeau

Inserm-EPHE-University of Caen/Basse-Normandie, Caen, France

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K. Ray Chaudhuri

K. Ray Chaudhuri

Department of Neurology, National Parkinson Foundation Centre of Excellence, King's College Hospital, and King's Health Partners, London, UK

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David J. Brooks

David J. Brooks

Neurology Imaging Unit, Department of Medicine, Imperial College London, Hammersmith Hospital, London, UK

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Paul Edison

Corresponding Author

Paul Edison

Neurology Imaging Unit, Department of Medicine, Imperial College London, Hammersmith Hospital, London, UK

Corresponding author. Tel.: +44-(0)20 3313 3725; Fax: +44-(0)20 8383 1783.

E-mail address: [email protected]

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First published: 17 September 2014
Citations: 139

Abstract

Background

Alzheimer's disease (AD) and Parkinson's disease (PD) are the two common neurodegenerative diseases characterized by progressive neuronal dysfunction in the presence of pathological microglial activation.

Methods

10 AD, 10 mild cognitive impairment (MCI), 11 PD dementia (PDD), and 16 controls underwent magnetic resonance imaging, [11C](R)PK11195 (1-[2-chlorophenyl]-N-methyl-N-[1-methyl-propyl]-3-isoquinoline carboxamide), [11C]PIB (11C-Pittsburgh compound B), [18F]FDG-PET (18F-2-fluoro-2-deoxyglucose positron emission tomography) scans. Parametric images were interrogated using region of interest (ROI), biological parametric mapping (BPM) and statistical parametric mapping analysis, and neuropsychometric tests.

Results

Using BPM analysis, AD, MCI, and PDD subjects demonstrated significant correlation between increased microglial activation and reduced glucose metabolism (rCMRGlc). AD and MCI subjects also showed significant positive correlation between amyloid and microglial activation. Levels of cortical microglial activation were negatively correlated with Mini-Mental State Examination in both AD and PDD.

Conclusion

The significant inverse correlations between cortical levels of microglial activation and rCMRGlc in AD and PDD suggest cortical neuroinflammation may drive neuronal dysfunction in these dementias.