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 range of tau pathology; however, binding property of PBB3 to non-tau inclusions remains unknown. To clarify whether [11C]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 [11C]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 [11C]PBB3 at 10 nM demonstrated no significant binding in Lewy body disease cases. In contrast, significant autoradiographic binding of [11C]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 [11C]PBB3 in human PET scans is approximately 10 nM, the present data imply that α-synuclein pathology in Lewy body disease is undetectable by [11C]PBB3-PET, whereas those in a subset of MSA cases with high densities of glial cytoplasmic inclusions could be captured by this radioligand.
Original language | English (US) |
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Pages (from-to) | 884-892 |
Number of pages | 9 |
Journal | Movement Disorders |
Volume | 32 |
Issue number | 6 |
DOIs | |
State | Published - Jun 2017 |
Keywords
- Lewy body disease
- PBB3
- autoradiography
- multiple system atrophy
- α-synucleinopathy
ASJC Scopus subject areas
- Neurology
- Clinical Neurology