Journal Article Fluorescence and Autoradiographic Evaluation of Tau PET Ligand PBB3 to α-Synuclein Pathology

Koga, Shunsuke  ,  Ono, Maiko  ,  Sahara, Naruhiko  ,  Higuchi, Makoto  ,  W. Dickson, Dennis

32 ( 6 )  , pp.884 - 892 , 2017-04
ABSTRACT: Background: The tau PET ligand 2-((1E,3E)-4-(6-([11C]methylamino)pyridin-3-yl)buta-1,3-dienyl)benzo[d]thiazol-6-ol ([11C]PBB3) binds to a wide rangeof tau pathology; however, binding property of PBB3 tonon-tau inclusions remains unknown. To clarifywhether [11C]PBB3 binds to a-synuclein pathology,reactivity of PBB3 was assessed by in vitro fluorescenceand autoradiographic labeling of brain sectionsfrom a-synucleinopathies patients.Method: Of 10 pure Lewy body disease and 120 multiplesystem atrophy (MSA) cases in the Mayo Clinicbrain bank, we selected 3 Lewy body disease and 4MSA cases with a range of a-synuclein severity basedon the quantitative analysis of a-synuclein burden.PBB3 fluorescence labeling, double or single immunostainingfor a-synuclein and phospho-tau, Prussian bluestaining, and in vitro autoradiography with [11C]PBB3were performed for these selected samples.Results: PBB3 fluorescence labeled various asynucleinlesions including Lewy bodies, Lewy neurites,spheroids, glial cytoplasmic inclusions, and neuronalcytoplasmic inclusions. Meanwhile, autoradiographiclabeling with [11C]PBB3 at 10nM demonstrated no significantbinding in Lewy body disease cases. In contrast,significant autoradiographic binding of [11C]PBB3to the striatopallidal fibers was found in 2 MSA cases,which had high densities of glial cytoplasmic inclusionswithout tau or iron deposits in this region.Conclusions: Given that the maximum concentration of[11C]PBB3 in human PET scans is approximately 10 nM,the present data imply that a-synuclein pathology inLewy body disease is undetectable by [11C]PBB3-PET,whereas those in a subset of MSA cases with high densitiesof glial cytoplasmic inclusions could be capturedby this radioligand. VC 2016 International Parkinson andMovement Disorder SocietyKey Words: Lewy body disease; multiple systematrophy; a-synucleinopathy; PBB3; autoradiography

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