Fluorescence and autoradiographic evaluation of tau PET ligand PBB3 to α‐synuclein pathology

Background : The tau PET ligand 2‐((1E,3E)‐4‐(6‐([ 11 C]methylamino)pyridin‐3‐yl)buta‐1,3‐dienyl)benzo[d]thiazol‐6‐ol ([ 11 C]PBB3) binds to a wide range of tau pathology; however, binding property of PBB3 to non‐tau inclusions remains unknown. To clarify whether [ 11 C]PBB3 binds to α‐synuclein pathology, reactivity of PBB3 was assessed by in vitro fluorescence and autoradiographic labeling of brain sections from α‐synucleinopathies patients. Method : Of 10 pure Lewy body disease and 120 multiple system atrophy (MSA) cases in the Mayo Clinic brain bank, we selected 3 Lewy body disease and 4 MSA cases with a range of α‐synuclein severity based on the quantitative analysis of α‐synuclein burden. PBB3 fluorescence labeling, double or single immunostaining for α‐synuclein and phospho‐tau, Prussian blue staining, and in vitro autoradiography with [ 11 C]PBB3 were performed for these selected samples. Results : PBB3 fluorescence labeled various α‐synuclein lesions including Lewy bodies, Lewy neurites, spheroids, glial cytoplasmic inclusions, and neuronal cytoplasmic inclusions. Meanwhile, autoradiographic labeling with [ 11 C]PBB3 at 10 nM demonstrated no significant binding in Lewy body disease cases. In contrast, significant autoradiographic binding of [ 11 C]PBB3 to the striatopallidal fibers was found in 2 MSA cases, which had high densities of glial cytoplasmic inclusions without tau or iron deposits in this region. Conclusions : Given that the maximum concentration of [ 11 C]PBB3 in human PET scans is approximately 10 nM, the present data imply that α‐synuclein pathology in Lewy body disease is undetectable by [ 11 C]PBB3‐PET, whereas those in a subset of MSA cases with high densities of glial cytoplasmic inclusions could be captured by this radioligand. © 2017 International Parkinson and Movement Disorder Society