Post-mortem validation of in vivo TSPO PET as a microglial biomarker

Area of Science:

• Neuroscience
• Molecular Imaging
• Neuropathology

Background:

• Neuroinflammation is a hallmark of neurodegenerative diseases.
• Positron emission tomography (PET) with translocator protein (TSPO) radioligands, such as 11C-PK11195, is used to quantify neuroinflammation in vivo.
• The precise cellular source of altered TSPO binding in disease states remains debated and requires neuropathological confirmation.

Purpose of the Study:

• To investigate the cellular substrate of 11C-PK11195 PET binding in vivo.
• To test the hypothesis that 11C-PK11195 PET reflects microglial activation in progressive supranuclear palsy (PSP).

Main Methods:

• Utilized 11C-PK11195 PET imaging data from individuals with PSP-Richardson's syndrome (n=8) and post-mortem brain tissue analysis.
• Performed cell-type specific TSPO expression analysis and quantified microgliosis in multiple brain regions.
• Employed double-immunofluorescence labeling for TSPO and cell-specific markers.

Main Results:

• TSPO expression was detected in microglia, astrocytes, and endothelial cells.
• Microglial TSPO levels and burden were significantly elevated in PSP donors compared to controls (n=3).
• A strong positive correlation was found between ante-mortem 11C-PK11195 binding and post-mortem measures of phagocytic microglia (CD68+) and microglial TSPO levels.

Conclusions:

• In vivo disease-related changes in 11C-PK11195 binding are predominantly driven by microglia.
• TSPO PET imaging can serve as a valuable biomarker for microglia-mediated neuroinflammation in tauopathies.
• This study provides neuropathological validation for interpreting TSPO PET findings in the context of microglial responses.