Tau Imaging in the 4-Repeat-Tauopathies Progressive Supranuclear Palsy and Corticobasal Syndrome

Abstract

Background and Objectives To evaluate tau PET using 11C-pyridinyl-butadienyl-benzothiazole 3 (11C-PBB3) in the 4-repeat (4R)-tauopathies progressive supranuclear palsy (PSP) and corticobasal syndrome (CBS). Methods Retrospective analysis of 11C-PBB3 PET in 2, 7, and 2 patients with CBS, PSP, and Alzheimer dementia (AD), respectively. Normalized 11C-PBB3 uptake in clusters with significant hypometabolism on 18F-FDG-PET and corresponding atlas-based volumes of interest was compared between diagnostic groups. Results In accordance with visually appreciable group differences, 11C-PBB3 uptake was significantly higher in dorsolateral frontal and motor cortex in CBS patients and frontal and temporal cortices in AD patients as compared with PSP patients. Patients with PSP showed mildly but significantly higher uptake in midbrain compared with AD patients. Conclusions In line with known neuropathological changes, the spatial pattern and magnitude of 11C-PBB3 tau binding differ between CBS, PSP, and AD, which may be of diagnostic utility. Thus, 11C-PBB3 offers a promising lead structure for development of ligands for tau imaging, including 4R-tauopathies.

Imaging pathological tau in atypical parkinsonisms: A review

“…This is consistent with CBD/S pathology which is hallmarked by asymmetric symptomology. In PSP patients, [11C]PBB3 uptake is heightened in the midbrain and thalamus compared to AD and CBS patients [67] . This finding is consistent with the neuropathological distribution of PSP-tau inclusions [9] , [68] .…”

“…When tested in CBS patients, [11C]PBB3 binding is observed extensively in the dorsal frontal, motor, and premotor cortices contralateral to the clinically more affected side [67] . This is consistent with CBD/S pathology which is hallmarked by asymmetric symptomology.…”

Clinical validity of increased cortical binding of tau ligands of the THK family and PBB3 on PET as biomarkers for Alzheimer’s disease in the context of a structured 5-phase development framework

“…To the best of our knowledge, no study has yet attempted to assess the accuracy of PBB3, although the evidence so far imply a good accuracy for discrimination of HCs and clinically diagnosed AD patients and a different regional pattern of binding for non-AD neurodegenerative diseases [27,[47][48][49][50][51][52].…”

Complementary Utility of Dopamine Transporter and Tau PET Imaging in the Diagnosis of Progressive Supranuclear Palsy

“…7,8 The most commonly affected areas include the putamen, globus pallidus, thalamus, subthalamic nucleus, midbrain (red nucleus and substantia nigra), dentate nucleus, parietal gray matter, and the frontoparietal white matter. [8][9][10] Differently from PSP, MSA is characterized by oligodendroglial cytoplasmic inclusions, which contain misfolded hyperphosphorylated α-synuclein, but not tau aggregates. 1 Although the patient's clinical manifestations (no ocular motor dysfunction) did not allow a definite diagnosis, the results of PET imaging using 3 different radiotracers suggested PSP.…”

“…Tau PET imaging studies have consistently shown an increased tau accumulation in the brain of patients with PSP, corresponding to overrepresentation of tau isoforms containing 4-repeat domains in autopsy series. 7,8 The most commonly affected areas include the putamen, globus pallidus, thalamus, subthalamic nucleus, midbrain (red nucleus and substantia nigra), dentate nucleus, parietal gray matter, and the frontoparietal white matter. [8][9][10] Differently from PSP, MSA is characterized by oligodendroglial cytoplasmic inclusions, which contain misfolded hyperphosphorylated α-synuclein, but not tau aggregates.…”