Presenter of 1 Presentation
MAPPING AND UNDERSTANDING TAU PATHOLOGY IN FTD SUBTYPES AND AD USING THE TAU PET TRACER PI2620.
Abstract
Aims
Tauopathies display distinct filament folds of abnormal tau protein of 3R and 4R isoforms. While AD expresses both 4R and 3R isoforms, CBD and PSP express mainly the 4R form. AD and CBD Tau fibrils structures have been determined and cryoEM analyses enabled to determine the theoretical binding sites of different Tau PET tracers on these various tau fibrils, whereas PSP tau fibrils remain undescribed. Objectives: The aim of this study was to characterize and better understand the differences in tau pathology between CBD, PSP and AD using the tau PET tracer 3H-PI2620.
Methods
On AD, CBD, PSP and control postmortem human brain tissue, we performed saturation and competition binding assays on frontal cortex. Regional distribution was also carried out on human brain homogenates of AD, PSP, CBD and control cases. We compared immunostaining and 3H-PI2620 autoradiography on frozen adjacent sections of frontal cortex and putamen.
Results
3H-PI2620 displayed two binding sites for AD and CBD but only one for PSP. Bmax values were higher in AD compared to CBD and PSP respectively. However 3H-PI2620 bound with similar high affinities in the three tauopathies. In AD and CBD unlabelled PI2620 competed with 3H-PI2620 for two binding sites but only for one in PSP.
Conclusions
In this study we observed differences in 3H-PI2620 binding properties between the tauopathies and ongoing studies will further unravel the interactions between the different hallmarks inducing the complexity of these tauopathies