LAUSR

Corticobasal degeneration (CBD) is a rapidly progressive parkinsonism typically associated with highly asymmetric cortical signs including apraxia, language impairment, cortical sensory deficit, and myoclonus. Pathologically there are straight filaments of tau associated with ballooned neurons in cortical gray matter and striatum, as well as astrocytic plaques, threads, and tangles. These filaments are predominantly formed by 4-repeat (4R) tau isoforms. Premortem diagnostic accuracy is lower than for other types of parkinsonism, with a differential that includes Alzheimer’s disease, Parkinson’s disease, frontotemporal dementia, and progressive supranuclear palsy. PET imaging, by demonstrating the specific deposition and distribution of abnormal tau, may help with diagnosis, but findings from tau imaging are variable. We report a case of corticobasal syndrome (CBS) with specific uptake of the tau tracer C-phenyl/pyridinyl-butadienyl-benzothiazole/benzothiazolium 3 (C-PBB3) (Fig 1a). This man presented at age 67 with a 3-year history of motor dysfunction. Initial examination revealed left side rigidity, stimulus-evoked myoclonus and apraxia, and mild cognitive dysfunction (MoCA 21). During the next year prior to his PET study, he developed increasing cognitive difficulty and impulsivity, cortical sensory deficit, and alien limb phenomenon. His MoCA and Dementia Rating Scale-2 (DRS-2) at time of scan were 14 and 62, respectively. He continued to deteriorate, became wheelchair bound with limited verbal output, asymmetric rigidity and dystonia, and died 2 years following PET. Neither amyloid imaging nor autopsy was performed. C-PBB3 PET performed approximately 4 years after symptom onset and quantified with nondisplaceable binding potential and cerebellar white matter as reference region revealed asymmetric bilateral binding, greater on the right, in frontal, parietal, temporal, and occipital cortex, caudate, thalamus, globus pallidus, and ventral striatum. In comparison to controls (n = 7) of similar age (mean = 65 years, SD = 10.8), C-PBB3 binding was increased by ≥2 SD in the bilateral globus pallidus, right insula, and right temporal lobe (Fig 1b). Binding was bilaterally increased in the motor cortex of the CBS subject, more on the right. This increase was < 2 SD of healthy control values, likely reflecting the small sample size and cortical atrophy in the CBS subject. Prior studies with F-AV-1451 in pathologically confirmed CBD reported uptake in cortex and basal ganglia, which correlated with postmortem 4R tau burden, but not with postmortem autoradiography, and concluded that F-AV-1451 probably binds to a small fraction of 4R tau burden. Smith and colleagues found F-AV-1451 imaging differentiated CBD from Alzheimer Disease (AD) and Progressive Supranuclear Palsy (PSP); however, cortical uptake did not correlate with atrophy on MRI or hypometabolism on fluoro-2-deoxyglucose (FDG) PET. Cho and colleagues reported asymmetric uptake in subcortical regions including precentral white matter in 6 CBS cases versus 20 controls. Uptake in precentral white matter correlated with motor symptoms, but overlapped with control values. Our findings are consistent with those of Maruyama and colleagues. Ono and colleagues compared postmortem binding of C-PBB3 and F-AV-1451 using autoradiography. They found strong binding of C-PBB3 to astrocytic plaques, coiled bodies, and argyrophilic threads in CBD, supporting reactivity with 4R aggregates. In contrast, weaker binding with only faint fluorescence was found with F-AV-1451. To date, results from F-AV-1451 appear inconsistent, with low sensitivity for the 4R aggregates found in CBD in vitro and variable results in vivo. C-PBB3 in PSP showed specific binding in areas where the highest tau burden is expected and was higher in more advanced cases. However, binding was also observed in synucleinopathies, questioning its specificity for tau. In CBD, C-PBB3 may show specific binding that correlates with the clinical manifestations and asymmetric characteristics of CBS, but further studies are needed.