Effect of alpha‐Synuclein on the binding of [18F]MK‐6240 and [18F]AV‐1451

Background Binding in alpha-synuclein containing brain regions have been described for both Flortaucipir ([18F]AV-1451) and [18F]MK-6240. Here we assessed whether alpha-Synuclein constitutes a target these tau imaging agents. Method We used autoradiographic dot blot to validate specific evaluate off-target interactions of [18F]MK-6240 [18F]AV-1451 using sarkosyl-insoluble extracts from PSP, CBD, PiD, AD cortical tissue which contain fibrillar forms tau. Tissue concentrations are orders magnitude lower than NFTs leading us use recombinant PFFs potential interactions. Briefly, 1:100 dilutions each preparation were incubated with 82 fmol mass 30uL total volume. Samples 90 minutes at 37°C. Reactions terminated by pipetting the solution triplicate onto glass fiber filter held within 96-well dot-blot aspiration device samples immobilized. Unbound ligand was washed three times ice cold PBS. The filters transferred cassette exposure film activity photostimulated luminescence units per mm2 calculated ImageJ software v.1.8.0. Result Disintegrations corrected decay normalized cerebellar ligands. demonstrated high specificity, binding subject trypsin treatment. similar native trypsinized extracts, while also showing overlapping profiles human but not mouse PFFs. Conclusion binds as it does AD-tau PHFs. Future experiments should assess patient derived aggregates off [18F]AV-1451.