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Simultaneous Imaging of Microglial Dynamics and Neuronal Activity in Awake Mice
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Early and Longitudinal Microglial Activation but Not Amyloid Accumulation Predicts Cognitive Outcome in PS2APP Mice

Carola Focke1, Tanja Blume1,2, Benedikt Zott3

  • 1Department of Nuclear Medicine, University Hospital of Munich, LMU Munich, Munich, Germany.

Journal of Nuclear Medicine : Official Publication, Society of Nuclear Medicine
|September 29, 2018
PubMed

Insights

Continuing microglial activation, measured by TSPO PET, is linked to better cognitive function in Alzheimer's disease (AD) mouse models. This suggests neuroinflammation plays a protective role in preserving cognition during AD progression.

Area of Science:

  • Neuroscience
  • Medical Imaging
  • Alzheimer's Disease Research

Background:

  • Neuroinflammation's role in Alzheimer's Disease (AD) is complex, with potential beneficial or detrimental impacts on cognition.
  • Positron Emission Tomography (PET) imaging of 18-kDa translocator protein (TSPO) allows in vivo monitoring of microglial activation.

Purpose of the Study:

  • To investigate the longitudinal relationship between neuroinflammation (TSPO PET), amyloid burden, and cognitive outcomes in an AD mouse model.
  • To correlate in vivo PET findings with ex vivo immunohistochemical markers of neuroinflammation and synaptic integrity.

Main Methods:

  • Serial PET scans measuring TSPO and amyloid were performed on PS2APP mice from 8 to 13 months of age.
  • Cognitive function was assessed using the water maze test.
  • Immunohistochemistry was used to analyze microglia, amyloid deposition, and synaptic density post-mortem.

Main Results:

  • Higher TSPO expression at 8 months predicted better cognitive performance and higher synaptic density at 13 months.
  • The progression of TSPO activation over time showed a moderate association with preserved cognition.
  • Amyloidosis levels did not correlate with cognitive outcomes at any time point.

Conclusions:

  • Early and sustained microglial activation, as indicated by TSPO PET, appears to be neuroprotective in this AD mouse model.
  • This study highlights the potential of longitudinal TSPO PET imaging to track neuroinflammatory responses relevant to cognitive function in AD.
Keywords:
TSPO PETamyloid PETneuroinflammationsynaptic densitywater maze

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