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

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.