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.

The Role of Hub and Spoke Regions in Theory of Mind in Early Alzheimer’s Disease and Frontotemporal Dementia

“…An open question remains regarding the relative importance of each of these regions in leading to ToM deficits across different clinical conditions and the ability of functional imaging to capture those changes more relevant to ToM performance in the earliest phases of the neurodegenerative process. Studies using brain 18 F-fluorodeoxyglucose positron emission tomography ( 18 F-FDG-PET) and tau markers have shown a negative correlation between tau deposition and cerebral metabolism in the right temporal, parietal and frontal lobes in a cohort of 100 Alzheimer's disease (AD) patients, confirming the clinical relevance of these regions in AD and suggesting that functional imaging can capture degeneration in these areas in AD [7,8]. Moreover, functional magnetic resonance imaging (fMRI) studies on functional connectivity [9] have provided evidence of the existence of brain networks engaged in different cognitive function, such as the default mode network (DMN), comprehensive of the mPFC and PCC [10], associated with internal processing (i.e., selfreferential thinking or thinking about the future) [11]; the executive control network (ECN), of which changes have been reported in mild cognitive impairment (MCI) [12], AD [13] and non-demented patients with late-life depression [14]; as well as the salience network (SN), responsible for detecting and incorporating sensory and emotional stimuli, both in healthy subjects and in neuropsychiatric conditions, which is located in the ventral and anterior insula and includes the amygdala, thalamus, striatum and hypothalamus [15,16].…”

Molecular imaging biomarkers in familial frontotemporal lobar degeneration: Progress and prospects

“…Frontotemporal lobar degeneration with MAPT mutations is regarded as tauopathy ( 32 ), and tau PET provides an effective way to explore biomarkers for multiform tau pathologies in a homogeneous patient group ( 33 ). Most individuals with MAPT mutations inside exon 10 (i.e., P301L, S305N, N279K) and intron 10 (i.e., IVS 10 + 16) had 4R tau pathology, while with MAPT mutations outside exon 10 (i.e., V337M, R406W, Q351R) had 3R/4R paired helical filament tau pathology ( 34 ).…”

Dissecting the Many Faces of Frontotemporal Dementia: An Imaging Perspective

“…In the last few years, advanced neuroimaging techniques have gone beyond the mere neuroanatomical description of frontotemporal atrophy or hypometabolism in FTD patients, and have helped in increasing the diagnostic accuracy, in disentangling the features associated with monogenic disease, in describing the earliest changes occurring in the prodromal phases, and in forecasting disease progression [ 10 ]. Moreover, new positron emission tomography tracers provide key information to define the underlying neuropathology [ 11 , 12 , 13 , 14 , 15 ]. These neuroimaging developments have contributed to the exploration of FTD pathogenesis and to the identification of novel potential biomarkers.…”