Abstract
Ironically, population aging which is considered a public health success has been accompanied by a myriad of new health challenges, which include neurodegenerative disorders (NDDs), the incidence of which increases proportionally to age. Among them, Alzheimer’s disease (AD) and Parkinson’s disease (PD) are the most common, with the misfolding and the aggregation of proteins being common and causal in the pathogenesis of both diseases. AD is characterized by the presence of hyperphosphorylated τ protein (tau), which is the main component of neurofibrillary tangles (NFTs), and senile plaques the main component of which is β-amyloid peptide aggregates (Aβ). The neuropathological hallmark of PD is α-synuclein aggregates (α-syn), which are present as insoluble fibrils, the primary structural component of Lewy body (LB) and neurites (LN). An increasing number of non-invasive PET examinations have been used for AD, to monitor the pathological progress (hallmarks) of disease. Notwithstanding, still the need for the development of novel detection tools for other proteinopathies still remains. This review, although not exhaustively, looks at the timeline of the development of existing tracers used in the imaging of Aβ and important moments that led to the development of these tracers.
Highlights
Of all the causes of dementia, Alzheimer’s disease (AD) stands in first place and makes up the largest part—about two-thirds—of all differential diagnoses [1,2,3], and it is the most common form of dementia in persons older than 65 years [4]
Positron emission tomography (PET) imaging especially, which is superior to other imaging techniques in terms of sensitivity, since only picomolar concentrations of the radiotracers are required allows to visualize, characterize and quantify physiological activities at molecular and cellular levels [29,30]
Introduction of a secondary alcohol in the fluoroethoxy chain in BF-170 and the monomethylation [18F]THK-5117 and dimethylation [18F]THK-5105 (Figure 5) of the aniline moiety gave tracers with higher in vitro affinities (Kd) for both synthetic HITP tau fibrils and for human ADPHF tau aggregates than [18F]THK-523: they showed a 16-fold and 32-fold increase in affinity for human AD-paired helical filaments (PHF) tau aggregates in comparison to their direct predecessor [18F]THK-523, a higher in vitro selectivity for tau versus Aβ; a coincidence with Gallyas-Braak staining and immunoreactive tau staining in autoradiography staining of human AD brain sections but not with the distribution of
Summary
Of all the causes of dementia, AD stands in first place and makes up the largest part—about two-thirds—of all differential diagnoses [1,2,3], and it is the most common form of dementia in persons older than 65 years [4]. Positron emission tomography (PET) imaging especially, which is superior to other imaging techniques in terms of sensitivity, since only picomolar concentrations of the radiotracers are required allows to visualize, characterize and quantify physiological activities at molecular and cellular levels [29,30] It may serve as an important diagnostic tool in the field of drug discovery and development, in order to monitor disease progression and the interaction of ligands with their targets. 25, 977 with other amyloid proteins like Aβ plaque and tau fibrils tracer, selectivity for α-syn aggregates over the others is a desired quality This explains why non-selective ligands are more common than selective tracers [79,80,81,82]. Radioisotopes [81,85,86]
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