[¹⁸F]-AV-1451 binding profile in chronic traumatic encephalopathy: a postmortem case series

Area of Science:

• Neuroscience
• Neuropathology
• Radiochemistry

Background:

• Chronic traumatic encephalopathy (CTE) is a neurodegenerative disease linked to repetitive head trauma.
• Currently, definitive CTE diagnosis requires post-mortem examination, highlighting the need for in vivo biomarkers.
• The PET tracer AV-1451 (Flortaucipir) binds well to tau in Alzheimer's disease but its utility in CTE is unknown.

Purpose of the Study:

• To investigate the binding characteristics of the PET tracer [18F]-AV-1451 in pathologically confirmed CTE post-mortem brain tissue.
• To assess the potential of AV-1451 as an in vivo biomarker for CTE tau pathology.

Main Methods:

• Post-mortem brain tissue from 5 CTE cases (stages II-IV) underwent [18F]-AV-1451 autoradiography, tau immunohistochemistry, Western blotting, and tau seeding assays.
• Brain regions analyzed included hippocampus, temporal cortex, frontal cortex, parietal cortex, and occipital cortex.
• Cases with significant co-existing Alzheimer's disease pathology were excluded.

Main Results:

• Autoradiography revealed minimal [18F]-AV-1451 binding to tau aggregates in CTE brains, despite abundant tau pathology.
• A strong signal was observed in the choroid plexus and meninges, attributed to off-target binding in leptomeningeal melanocytes.
• Western blotting and tau seeding assays indicated lower levels of abnormal tau in CTE compared to Alzheimer's disease.

Conclusions:

• The PET tracer AV-1451 demonstrates limited utility for the selective and reliable in vivo detection of tau aggregates in CTE.
• Differential binding of AV-1451 across tauopathies may stem from disease-specific tau conformations.
• Further research is needed to develop effective in vivo biomarkers for CTE.