Tau Biomarkers in Dementia: Positron Emission Tomography Radiopharmaceuticals in Tauopathy Assessment and Future Perspective

Abstract

Abnormal accumulation of Tau protein is closely associated with neurodegeneration and cognitive impairment and it is a biomarker of neurodegeneration in the dementia field, especially in Alzheimer's disease (AD); therefore, it is crucial to be able to assess the Tau deposits in vivo. Beyond the fluid biomarkers of tauopathy described in this review in relationship with the brain glucose metabolic patterns, this review aims to focus on tauopathy assessment by using Tau PET imaging. In recent years, several first-generation Tau PET tracers have been developed and applied in the dementia field. Common limitations of first-generation tracers include off-target binding and subcortical white-matter uptake; therefore, several institutions are working on developing second-generation Tau tracers. The increasing knowledge about the distribution of first- and second-generation Tau PET tracers in the brain may support physicians with Tau PET data interpretation, both in the research and in the clinical field, but an updated description of differences in distribution patterns among different Tau tracers, and in different clinical conditions, has not been reported yet. We provide an overview of first- and second-generation tracers used in ongoing clinical trials, also describing the differences and the properties of novel tracers, with a special focus on the distribution patterns of different Tau tracers. We also describe the distribution patterns of Tau tracers in AD, in atypical AD, and further neurodegenerative diseases in the dementia field.

Keywords: Alzheimer’s disease; PET; Tau PET; Tau biomarkers; Tau tracers; [18F]Flortaucipir; dementia; first-generation Tau tracers; second-generation Tau tracers; tauopathy.

Figure 1

A figure published in a previous paper of our research group, focused on the comparison of brain glucose metabolism and T-Tau level in CSF in AD. Three-dimensional brain rendering showing in (a) the cluster obtained in SPM regression analysis of T-Tau in AD (red). In (b), we show the cluster obtained from the comparison of HC and AD subjects (hypometabolism in AD, green). In (c), both clusters are merged in a single image, showing the overlap of the temporal and parietal cortices (see text). AD: Alzheimer’s disease; HC: healthy controls. Image source: Brain metabolic correlates of CSF Tau protein in a large cohort of Alzheimer’s disease patients: A CSF and [¹⁸F]FDG PET study. A. Chiaravalloti et al./Brain Research 1678 (2018) 116–122 [60].