Ryuichi Harada1,2, Aiko Ishiki2, Hideaki Kai3, Naomi Sato4, Katsutoshi Furukawa2,5, Shozo Furumoto6, Tetsuro Tago7, Naoki Tomita2, Shoichi Watanuki6, Kotaro Hiraoka6, Yoichi Ishikawa6, Yoshihito Funaki6, Tadaho Nakamura8, Takeo Yoshikawa9, Ren Iwata6, Manabu Tashiro6, Hironobu Sasano4, Tetsuyuki Kitamoto3, Kazuhiko Yanai9,6, Hiroyuki Arai2, Yukitsuka Kudo2, Nobuyuki Okamura6,8. 1. Department of Pharmacology, Tohoku University School of Medicine, Sendai, Japan dragon1@med.tohoku.ac.jp. 2. Department of Gerontology and Geriatrics, Institute of Development, Aging and Cancer, Tohoku University, Sendai, Japan. 3. Department of Neurological Science, Tohoku University School of Medicine, Sendai, Japan. 4. Department of Pathology, Tohoku University School of Medicine, Sendai, Japan. 5. Division of Community Medicine, Faculty of Medicine, Tohoku Medical and Pharmaceutical University, Sendai, Japan. 6. Cyclotron and Radioisotope Center, Tohoku University, Sendai, Japan. 7. Research Team for Neuroimaging, Tokyo Metropolitan Institute of Gerontology, Tokyo, Japan; and. 8. Division of Pharmacology, Faculty of Medicine, Tohoku Medical and Pharmaceutical University, Sendai, Japan. 9. Department of Pharmacology, Tohoku University School of Medicine, Sendai, Japan.
Abstract
Clinical PET studies using 18F-THK5351 have demonstrated significant tracer retention in sites susceptible to tau burden in Alzheimer disease (AD). However, the in vivo PET signal to reflect tau aggregates remains controversial. Methods: We examined the spatial pattern of tracer binding, amyloid-β, tau, and gliosis in an autopsy-confirmed AD patient who underwent 18F-THK5351 and 11C-Pittsburgh compound B PET before death. Results: Regional in vivo 18F-THK5351 retention was significantly correlated with the density of tau aggregates in the neocortex and monoamine oxidase-B in the whole brain, but not correlated with that of insoluble amyloid-β. Furthermore, significant association was observed between the density of tau aggregates, monoamine oxidase-B, and glial fibrillary acidic protein, suggesting that neocortical tau would strongly influence the formation of reactive astrocytes. Conclusion: 18F-THK5351 PET may have limited utility as a biomarker of tau pathology in AD; however, it could be used to monitor the neuroinflammatory processes in the living brain.
Clinical PET studies using 18F-THK5351 have demonstrated significant tracer retention in sites susceptible to tau burden in Alzheimer disease (AD). However, the in vivo PET signal to reflect tau aggregates remains controversial. Methods: We examined the spatial pattern of tracer binding, amyloid-β, tau, and gliosis in an autopsy-confirmed ADpatient who underwent 18F-THK5351 and 11C-Pittsburgh compound B PET before death. Results: Regional in vivo 18F-THK5351 retention was significantly correlated with the density of tau aggregates in the neocortex and monoamine oxidase-B in the whole brain, but not correlated with that of insoluble amyloid-β. Furthermore, significant association was observed between the density of tau aggregates, monoamine oxidase-B, and glial fibrillary acidic protein, suggesting that neocortical tau would strongly influence the formation of reactive astrocytes. Conclusion: 18F-THK5351 PET may have limited utility as a biomarker of tau pathology in AD; however, it could be used to monitor the neuroinflammatory processes in the living brain.
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