Abstract
IntroductionThe introduction of tau imaging agents such as 18F-THK523 offers new hope for the in vivo assessment of tau deposition in tauopathies such as Alzheimer’s disease (AD), where preliminary 18F-THK523-PET studies have demonstrated significantly higher cortical retention of 18F-THK523 in AD compared to age-matched healthy individuals. In addition to AD, tau imaging with PET may also be of value in assessing non-AD tauopathies, such as corticobasal degeneration (CBD), progressive supranuclear palsy (PSP) and Pick’s disease (PiD).MethodsTo further investigate the ability of THK523 to recognize tau lesions, we undertook immunohistochemical and fluorescence studies in serial brain sections taken from individuals with AD (n = 3), CBD (n = 2), PSP (n = 1), PiD (n = 2) and Parkinson’s disease (PD; n = 2). In addition to the neuropathological analysis, one PSP patient had undergone a 18F-THK523 PET scan 5 months before death.ResultsAlthough THK523 labelled tau-containing lesions such as neurofibrillary tangles and neuropil threads in the hippocampus and frontal regions of AD brains, it failed to label tau-containing lesions in non-AD tauopathies. Furthermore, though THK523 faintly labelled dense-cored amyloid-β plaques in the AD frontal cortex, it failed to label α-synuclein-containing Lewy bodies in PD brain sections.ConclusionThe results of this study suggest that 18F-THK523 selectively binds to paired helical filament tau in AD brains but does not bind to tau lesions in non-AD tauopathies, or to α-synuclein in PD brains.
Highlights
The introduction of tau imaging agents such as 18F-THK523 offers new hope for the in vivo assessment of tau deposition in tauopathies such as Alzheimer’s disease (AD), where preliminary 18F-THK523-Positron emission tomography (PET) studies have demonstrated significantly higher cortical retention of 18F-THK523 in AD compared to age-matched healthy individuals
Tau aggregation in this wide spectrum of tauopathies presents with different morphologies and ultrastructural conformations, which are probably attributable to the combinations of the different tau isoforms and a wide variety of posttranslation modifications [6,12]
To discern whether 18F-THK523 recognises non-AD tau aggregates in addition to Neurofibrillary tangle (NFT), we evaluated a series of brain sections from AD and non-AD tauopathies to evaluate the binding profile of 18F-THK523
Summary
The introduction of tau imaging agents such as 18F-THK523 offers new hope for the in vivo assessment of tau deposition in tauopathies such as Alzheimer’s disease (AD), where preliminary 18F-THK523-PET studies have demonstrated significantly higher cortical retention of 18F-THK523 in AD compared to age-matched healthy individuals. Whilst the underlying mechanism leading to tau accumulation remains unclear, it is thought to be related to several pathogenic events resulting in hyperphosphorylation, misfolding and aggregation of tau Tau aggregation in this wide spectrum of tauopathies presents with different morphologies (for example, NFTs in AD, astrocytes in CBD, globose tangles and thorny and tufted astrocytes in PSP and Pick bodies in PiD [6,7,8,9]) and ultrastructural conformations (for example, paired helical filaments in AD, straight filaments in PSP and twisted ribbons and random coils in PiD [6,10,11]), which are probably attributable to the combinations of the different tau isoforms and a wide variety of posttranslation modifications [6,12]. The differential diagnosis might require the development of selective tau radiotracers for each specific conformation of tau aggregates
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