ABILITY OF NEXT-GENERATION TAU PET TRACERS TO DISCRIMINATE ALZHEIMER’S DISEASE HISTOPATHOLOGY FROM OTHER DEMENTIAS
- Steven Y. Yap, United Kingdom
Abstract
Aims
A next generation of tau PET tracers for imaging of Alzheimer’s disease and other dementias has recently been developed. Whilst the new compounds have now entered clinical studies, there is limited information available to assess their suitability for clinical applications. Head-to-head comparisons are urgently needed to understand differences in the radiotracer binding profiles.
Methods
We characterised the binding of the tau tracers PI2620, RO948, MK6240 and JNJ067 in human post-mortem brain tissue from a cohort of 25 dementia cases and age-matched controls, using quantitative phosphorimaging with tritium labelled radiotracers in conjunction with phospho-tau specific immunohistochemistry.
Results
The four tau radiotracers depicted tau inclusions composed of paired helical filaments with high specificity, both in cases with Alzheimer’s disease and in primary tauopathy cases with concomitant Alzheimer’s disease pathology. In contrast, cortical binding to primary tauopathy cases without paired helical filament tau was found to be within the range of age-matched controls. In basal ganglia tissue, tracer binding was not reduced by heterologous blocking with the selective monoamine oxidase B inhibitor L-deprenyl.
Conclusions
The head-to-head comaprison of next-generation tau PET tracers demonstrates that all four radiotracers bind with high specificity to cortical PHF-tau, whereas tracer binding to cortical inclusions characteristic of primary tauopathies is low. Several limitations of the first generation of tau tracers, largely associated with MAO-B off-target binding, appear to have been overcome. Our results suggest that the new tau PET tracers are suitable tools for distinguishing Alzheimer’s disease from controls as well as other dementias with high robustness.