[18F]T807 ([18F]AV-1451) and Fluorescent Analog T726 Bind to PHF-Tau but Not TDP-43 in Alzheimer’s and FTD Post-Mortem Brain Tissue Sections

1083 Objectives The objective of this study was to determine if [18F]T807 and its fluorescent analog T726 bind to TDP-43 in AD and FTD post-mortem human brain tissue. Methods Tissue from 14 AD and 15 FTD cases as well as 1 normal control were selected for this study. Frontal, medial-temporal, parietal gyrus, amygdala, hippocampus, and entorhinal cortex were included for a total of over 50 brain slice sections analyzed. Fresh frozen brain sections were stained with phospho-Tau (AT8, AT100) and TDP-43 antibodies (TDP-43, and pTDP-43). Double or triple immunofluorescence staining using T726 was performed to investigate whether the observed signal from T726 co-localized with staining from PHF-Tau or TDP-43 antibodies. Additionally, autoradiography with [18F]T807 in the absence or presence of excess T807 was conducted to investigate the ability of [18F]T807 to label PHF-Tau or TDP-43 pathology in brain sections containing these aggregates. Results No co-localization of fluorescent signals occurred between T726 and TDP-43 antibodies in AD, FTD/PPA and FTLD-TDP cases. [18F]T807 produced intense and specific autoradiography signal in all tau-rich brain sections but not in TDP-43 positive/tau negative tissue. Conclusions Autoradiography experiments with [18F]T807 in AD and FTD as well as immunofluorescence studies with T726 suggest that no interference due to cross-reactivity with TDP-43 binding should occur when [18F]T807 is used to detect PHF-tau in human brain tissue.