Abstract Details

Title Influence of Neuroinflammation on Neuronal Function in Neurodegenerative Diseases: An 11C-(R)-PK11195 and 18F-FDG PET Study

Topic Aging and Dementia

Presentation(s) S44 - (-)

Poster/Presentation
Number 003

Objective

Background AD and PD are the two most common neurodegenerative diseases characterised by a progressive neuronal dysfunction. Neurinflammation is a common feature seen in different neurodegenerative diseases, and is characterised by microglial activation. 11C-®-PK11195 PET is a microglial imaging agent, while 18F-FDG PET measures the cerebral glucose metabolism.

Design/Methods 10 AD, 10, MCI, 5 non-demented PD, 7 PDD and 16 control subjects were recruited. Subjects underwent T1 and T2 MRI, 11C-®-PK11195 and 18F-FDG PET scans. Parametric images of 11C-®-PK11195 binding potential (BP) and rCMRGlc were interrogated using Region of Interest (ROI), Statistical Parametric Mapping (SPM) analysis, and voxel-voxel analysis using biological parametric mapping.

Results AD, MCI, PDD, and PD subjects demonstrated significant increase in microglial activation. As group, AD, PDD, and PD subjects also demonstrated reduction in glucose metabolism compared to the healthy control group. Higher whole cortical microglial activation in AD was correlated with reduced glucose metabolism in AD and PDD. At voxel level there were significant correlation between microglial activation, cognitive scores, and reduced cerebral glucose metabolism in different cortical regions.

Conclusions This has demonstrated significant microglial activation in AD, MCI, PDD, and PD subjects suggesting that this could be a common and an early phenomenon in neurodegenerative diseases. Significant correlation between microglial activation and rCMRGlc suggests cortical neuroinflammation could be associated with hippocampal neuronal damage and synaptic dysfunction, suggenting agents influencing microglial activation may have potential therapeutic benefit in neurodegenerative diseases.

Authors/Disclosures
Paul Edison, MBBS, PhD, FRCPI (Imperial College London) PRESENTER	No disclosure on file
Jay-Jiguang Zhu, MD, PhD, FAAN (Univ of Texas Health Science Center in Houston)	The institution of Dr. Zhu has received research support from Novocure, Inc. The institution of Dr. Zhu has received research support from Five Prime pharmaceutical. The institution of Dr. Zhu has received research support from Denovo, inc. The institution of Dr. Zhu has received research support from Boston Biomedical Sumitomo Dainippon Pharma Global Oncology. The institution of Dr. Zhu has received research support from CNS pharmaceutical. The institution of Dr. Zhu has received research support from ABM Therapeutics Corporation . The institution of Dr. Zhu has received research support from Chimerix Inc.
	No disclosure on file
David J. Brooks, MD, DSc, FRCP (Imperial College London)	No disclosure on file
	No disclosure on file

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