TY - JOUR
T1 - Assessing THK523 selectivity for tau deposits in Alzheimer's disease and non-Alzheimer's disease tauopathies
AU - Fodero-Tavoletti, Michelle T.
AU - Furumoto, Shozo
AU - Taylor, Leanne
AU - McLean, Catriona A.
AU - Mulligan, Rachel S.
AU - Birchall, Ian
AU - Harada, Ryuichi
AU - Masters, Colin L.
AU - Yanai, Kazuhiko
AU - Kudo, Yukitsuka
AU - Rowe, Christopher C.
AU - Okamura, Nobuyuki
AU - Villemagne, Victor L.
N1 - Funding Information:
We thank Fairlie Hinton and Geoff Pavey from the Victorian Brain Bank Network (VBBN) for sourcing and preparing the human brain tissue (HREC University of Melbourne 9414748). The VBBN is supported by The Florey Institute of Neuroscience and Mental Health, The Alfred and the Victorian Forensic Institute of Medicine, and it is funded by Australia’s National Health & Medical Research Council (NHMRC) and Parkinson’s Victoria. The research was supported in part by Alzheimer’s Drug Discovery Foundation Research Grant 20101208 AFTD and NHMRC project grant 1044361.
Publisher Copyright:
© 2014 Fodero-Tavoletti et al.
PY - 2014
Y1 - 2014
N2 - Introduction: 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. 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). Methods: To 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. Results: Although 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. Conclusion: The 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.
AB - Introduction: 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. 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). Methods: To 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. Results: Although 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. Conclusion: The 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.
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U2 - 10.1186/alzrt240
DO - 10.1186/alzrt240
M3 - Article
AN - SCOPUS:84989184669
VL - 6
JO - Alzheimer's Research and Therapy
JF - Alzheimer's Research and Therapy
SN - 1751-0147
IS - 1
M1 - 11
ER -