Objective: To assess in vivo, with molecular imaging the brain distribution of tau aggregates ([¹⁸F]AV1451 PET) and β-amyloid depositions ([¹⁸F]AV45 PET) in patients with Corticobasal Syndrome (CBS).

Background: CBS is a sporadic neurodegenerative disorder that causes accumulation of phosphorylated tau in neurons and glial cells. No mechanism-based treatments for CBS are available, and those treatments that exist are symptomatic. The prevention of tau aggregation and propagation is the focus of attempts to develop mechanism-based treatments for tauopathies. 

Methods: Six CBS patients (3M; mean age ±SD: 71.3±7.4 years; mean disease duration ±SD: 5.2±2.9 years) and 6 healthy controls (3M; mean age ±SD: 72.5±6.5 years) underwent one [¹⁸F]AV1451 PET, one [¹⁸F]AV45 PET scan and one 3-T MRI scan. Image processing was carried out using MIAKAT^TM.  Standardised uptake value ratio (SUVR) were generated for [¹⁸F]AV1451 and [¹⁸F]AV45 relative to cerebellum grey matter. 

Results: CBS patients showed 10-30% increases in cortical [¹⁸F]AV1451 uptake compared to the group of healthy controls consistent with increased tau deposition. In CBS patients, [¹⁸F]AV1451 SUVR were significantly increased in the medial frontal cortex (+10%; P<0.05), posterior medial frontal cortex (+13%; P<0.05), supplementary motor area (+21%; P<0.05), precentral gyrus (+17%; P<0.05), parietal lobe (+21%; P<0.05), parietal lobule (+30%; P<0.01), postcentral gyrus (+17%; P P<0.05), precuneous (+22%; P<0.05), cuneus (+22.2%; P<0.05), occipital fusiform gyrus (+26%; P<0.01) and lingual gyrus (+15%; P<0.05). Asymmetrical tau deposition with greater [¹⁸F]AV1451 retention contralateral to the most affected side was observed in CBS patients. Cortical and subcortical [¹⁸F]AV45 uptake was within normal levels in CBS patients.   

Conclusions: Cortical aggregates of tau pathology are present in CBS patients with low amyloid burden. In vivo imaging of tau aggregates with PET can aid in early diagnosis of CBS before extensive neuronal loss and clinical symptoms become evident. Additionally, it can also serve as an indicator of treatment efficacy for interventions aimed at preventing tau aggregate formation.

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MDS Abstracts - https://www.mdsabstracts.org/abstract/in-vivo-evaluation-of-tau-and-amyloid-pathology-in-corticobasal-syndrome/