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Updated: Mar 2, 2026
Hybrid PET/MRI Imaging of Alzheimer's Disease Based on 18F-AV-1451
Published on: April 18, 2025
Molecular imaging of neuroinflammation in Alzheimer's disease and mild cognitive impairment
Dunja Knezevic1, Romina Mizrahi1
1Institute of Medical Science, University of Toronto, Toronto, ON, Canada; Campbell Family Mental Health Research Institute, Centre for Addiction and Mental Health, Toronto, ON, Canada.
Abstract:
Neuroinflammatory changes have been demonstrated to be an important feature of Alzheimer's disease (AD); however, the exact role of neuroinflammation and its progression during disease is still not well understood. One of the main drivers of the neuroinflammatory process are microglial cells. Positron Emission Tomography allows for the quantification of microglial activation by labelling the Translocator Protein 18kDa (TSPO), which becomes overexpressed upon activation of microglial cells. Several radioligands have been designed to target TSPO and have been studied in-vivo in AD populations. While most studies have shown important increases in TSPO binding in AD populations compared to healthy volunteers, whether the neuroinflammatory progress occurs early on or later during disease is still unclear. In order to investigate the early changes in neuroinflammation, studies have sought to investigate microglial activation in patients with mild cognitive impairment (MCI), which is defined as a transitional stage between normal aging and dementia. In this prodromal population, conflicting results have been reported with some studies reporting increased binding in MCI, while others demonstrate no differences from controls. Here we review the TSPO PET studies in AD and MCI populations and discuss the important methodological considerations of imaging microglial activation.
Insights
Neuroinflammation, marked by microglial cell activation, is key in Alzheimer's disease (AD). Positron Emission Tomography (PET) studies using Translocator Protein 18kDa (TSPO) tracers show mixed results in early AD stages like mild cognitive impairment (MCI).
Area of Science:
- Neuroscience
- Radiology
- Immunology
Background:
- Neuroinflammation is a significant factor in Alzheimer's disease (AD) pathogenesis.
- Microglial cells are central players in the brain's inflammatory response.
- The precise timing and role of neuroinflammation in AD progression remain unclear.
Purpose of the Study:
- To review Positron Emission Tomography (PET) studies targeting Translocator Protein 18kDa (TSPO) in AD and mild cognitive impairment (MCI).
- To investigate the utility of TSPO PET imaging in understanding early neuroinflammatory changes.
- To discuss methodological considerations for accurately assessing microglial activation.
Main Methods:
- Review of in-vivo TSPO PET studies in AD and MCI populations.
- Quantification of microglial activation via TSPO radioligand binding.
- Comparison of TSPO binding in AD and MCI patients versus healthy controls.
Main Results:
- Most studies report increased TSPO binding in AD patients compared to controls.
- Results regarding TSPO binding in MCI patients are conflicting, with some showing increases and others no difference.
- The exact stage at which neuroinflammation occurs in AD progression is still debated.
Conclusions:
- TSPO PET imaging is a valuable tool for assessing microglial activation in neurodegenerative diseases.
- Further research and methodological standardization are needed to clarify the role of early neuroinflammation in AD.
- Understanding neuroinflammation in MCI is crucial for diagnosing and potentially treating AD in its prodromal stages.
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