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.
PY - 2014/2/26
Y1 - 2014/2/26
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.
UR - http://www.scopus.com/inward/record.url?scp=84989184669&partnerID=8YFLogxK
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 - 1758-9193
IS - 1
M1 - 11
ER -