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Microglial activation in Alzheimer's disease: an (R)-[¹¹C]PK11195 positron emission tomography study
Alie Schuitemaker1, Marc A Kropholler, Ronald Boellaard
1Department of Neurology and Alzheimer Center, VU University Medical Center, Amsterdam, the Netherlands. ASchuitemaker@zuwehofpoort.nl
Unlabelled:
Inflammatory mechanisms, like microglial activation, could be involved in the pathogenesis of Alzheimer's disease (AD). (R)-[(11)C]PK11195 (1-(2-chlorophenyl)-N-methyl-N-1(1-methylpropyl)-3-isoquinolinecarboxamide), a positron emission tomography (PET) ligand, can be used to quantify microglial activation in vivo. The purpose of this study was to assess whether increased (R)-[(11)C]PK11195 binding is present in AD and mild cognitive impairment (MCI), currently also known as "prodromal AD."
Methods:
Nineteen patients with probable AD, 10 patients with prodromal AD (MCI), and 21 healthy control subjects were analyzed. Parametric images of binding potential (BP(ND)) of (R)-[(11)C]PK11195 scans were generated using receptor parametric mapping (RPM) with supervised cluster analysis. Differences between subject groups were tested using mixed model analysis, and associations between BP(ND) and cognition were evaluated using Pearson correlation coefficients.
Results:
Voxel-wise statistical parametric mapping (SPM) analysis showed small clusters of significantly increased (R)-[(11)C]PK11195 BP(ND) in occipital lobe in AD dementia patients compared with healthy control subjects. Regions of interest (ROI)-based analyses showed no differences, with large overlap between groups. There were no differences in (R)-[(11)C]PK11195 BP(ND) between clinically stable prodromal AD patients and those who progressed to dementia, and BP(ND) did not correlate with cognitive function.
Conclusion:
Microglial activation is a subtle phenomenon occurring in AD.
Insights
Microglial activation, measured by (R)-[(11)C]PK11195 positron emission tomography (PET) scans, showed subtle increases in Alzheimer's disease (AD) patients but not in mild cognitive impairment (MCI). No significant correlations with cognitive function were found.
Area of Science:
- Neuroscience
- Radiochemistry
- Medical Imaging
Background:
- Microglial activation is implicated in Alzheimer's disease (AD) pathogenesis.
- (R)-[(11)C]PK11195 is a positron emission tomography (PET) ligand used to quantify in vivo microglial activation.
Purpose of the Study:
- To investigate increased (R)-[(11)C]PK11195 binding in AD and mild cognitive impairment (MCI), also known as prodromal AD.
- To assess microglial activation in early stages of AD.
Main Methods:
- Nineteen AD patients, 10 MCI patients, and 21 controls underwent PET scans with (R)-[(11)C]PK11195.
- Parametric images of binding potential (BP(ND)) were generated using receptor parametric mapping (RPM).
- Statistical parametric mapping (SPM) and region of interest (ROI) analyses were performed to compare groups and correlate with cognition.
Main Results:
- Voxel-wise SPM analysis revealed small clusters of increased (R)-[(11)C]PK11195 BP(ND) in the occipital lobe of AD patients compared to controls.
- ROI analyses showed no significant differences between groups, with substantial overlap.
- No differences in BP(ND) were observed between stable MCI and those progressing to dementia, nor did BP(ND) correlate with cognitive function.
Conclusions:
- Microglial activation is a subtle phenomenon observed in Alzheimer's disease.
- The study suggests limited utility of (R)-[(11)C]PK11195 PET for detecting microglial activation in MCI or correlating it with cognitive decline.
