Quantitative analysis of regional distribution of tau pathology with 11C-PBB3-PET in a clinical setting.

Purpose: The recent developments of tau-positron emission tomography (tau-PET) enable in vivo assessment of neuropathological tau aggregates. Among the tau-specific tracers, the application of 11C-pyridinyl-butadienyl-benzothiazole 3 (11C-PBB3) in PET shows high sensitivity to Alzheimer disease (AD)-related tau deposition. The current study investigates the regional tau load in patients within the AD continuum, biomarker-negative individuals (BN) and patients with suspected non-AD pathophysiology (SNAP) using 11C-PBB3-PET.
Materials and Methods: A total of 23 memory clinic outpatients with recent decline of episodic memory were examined using 11C-PBB3-PET. Pittsburg compound B (11C-PIB) PET was available for 17, 18F-flurodeoxyglucose (18F-FDG) PET for 16, and cerebrospinal fluid (CSF) protein levels for 11 patients. CSF biomarkers were considered abnormal based on Aβ42 (< 600 ng/L) and t-tau (> 450 ng/L). The PET biomarkers were classified as positive or negative using statistical parametric mapping (SPM) analysis and visual assessment. Using the amyloid/tau/neurodegeneration (A/T/N) scheme, patients were grouped as within the AD continuum, SNAP, and BN based on amyloid and neurodegeneration status. The 11C-PBB3 load detected by PET was compared among the groups using both atlas-based and voxel-wise analyses.
Results: Seven patients were identified as within the AD continuum, 10 SNAP and 6 BN. In voxel-wise analysis, significantly higher 11C-PBB3 binding was observed in the AD continuum group compared to the BN patients in the cingulate gyrus, tempo-parieto-occipital junction and frontal lobe. Compared to the SNAP group, patients within the AD continuum had a considerably increased 11C-PBB3 uptake in the posterior cingulate cortex. There was no significant difference between SNAP and BN groups. The atlas-based analysis supported the outcome of the voxel-wise quantification analysis.
Conclusion: Our results suggest that 11C-PBB3-PET can effectively analyze regional tau load and has the potential to differentiate patients in the AD continuum group from the BN and SNAP group.
Competing Interests: Christine A.F. von Arnim received honoraria from serving on the scientific advisory board of Nutricia GmbH (2014) and Honkong University Research council (2014) and has received funding for travel and speaker honoraria from Nutricia GmbH (2014–2015), Lilly Deutschland GmbH (2013–2016), Desitin Arzneimittel GmbH (2014), Biogen (2016-2018), Roche (2017-2018) and Dr. Willmar Schwabe GmbH & Co. KG (2014-2015). This does not alter our adherence to PLOS ONE policies on sharing data and materials. Makoto Higuchi and co-workers at National Institutes for Quantum and Radiological Science and Technology (QST) hold a patent on tau imaging agents (JP 5422782/EP 12 884 742.3), and QST made a license agreement with APRINOIA Therapeutics Inc. regarding this patent. This does not alter our adherence to PLOS ONE policies on sharing data and materials.