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Published on: June 14, 2018
Imaging of Microglial Activation in Alzheimer's Disease by [11C]PBR28 PET
Cornelius K Donat1, Nazanin Mirzaei1, Sac-Pham Tang2
1Division of Brain Sciences, Imperial College London, Hammersmith Hospital, London, UK.
Abstract:
Deficits in neuronal function and synaptic plasticity in Alzheimer's disease (AD) are believed to be linked to microglial activation. A hallmark of reactive microglia is the upregulation of mitochondrial translocator protein (TSPO) expression. Positron emission tomography (PET) is a nuclear imaging technique that measures the distribution of trace doses of radiolabeled compounds in the body over time. PET imaging using the 2nd generation TSPO tracer [11C]PBR28 provides an opportunity for accurate visualization and quantification of changes in microglial density in transgenic mouse models of Alzheimer's disease (AD). Here, we describe the methodology for the in vivo use of [11C]PBR28 in AD patients and the 5XFAD transgenic mouse model of AD and compare the results against healthy individuals and wild-type controls. To confirm the results, autoradiography with [3H]PBR28 and immunochemistry was carried out in the same mouse brains. Our data shows that [11C]PBR28 is suitable as a tool for in vivo monitoring of microglial activation and may be useful to assess treatment response in future studies.
Insights
Positron emission tomography (PET) with [11C]PBR28 effectively visualizes microglial activation in Alzheimer's disease (AD) models. This tracer may help monitor disease progression and treatment efficacy in future Alzheimer's studies.
Area of Science:
- Neuroscience
- Medical Imaging
- Biochemistry
Background:
- Alzheimer's disease (AD) is associated with neuronal dysfunction and impaired synaptic plasticity.
- Microglial activation, indicated by increased mitochondrial translocator protein (TSPO) expression, is a key feature in AD pathology.
- Positron emission tomography (PET) enables in vivo imaging of molecular targets.
Purpose of the Study:
- To evaluate the utility of the TSPO tracer [11C]PBR28 for in vivo imaging of microglial activation in Alzheimer's disease.
- To compare [11C]PBR28 PET imaging results in AD patients and a 5XFAD mouse model with healthy controls and wild-type littermates.
Main Methods:
- In vivo PET imaging using the TSPO tracer [11C]PBR28 was performed in AD patients and 5XFAD mice.
- Comparisons were made against healthy individuals and wild-type controls.
- Autoradiography with [3H]PBR28 and immunohistochemistry were used for ex vivo validation in mouse brains.
Main Results:
- [11C]PBR28 PET imaging successfully visualized and quantified changes in microglial density in AD models.
- Results from PET imaging correlated with ex vivo autoradiography and immunohistochemistry findings.
- [11C]PBR28 demonstrated suitability for in vivo monitoring of microglial activation.
Conclusions:
- [11C]PBR28 is a valuable tool for in vivo assessment of microglial activation in Alzheimer's disease.
- This PET tracer holds potential for monitoring disease progression and evaluating therapeutic interventions in AD research.
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