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.

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.