Hyon Lee1, Seongho Seo2, Sang-Yoon Lee2, Hye Jin Jeong3, Sung-Ho Woo3, Kyoung-Min Lee4, Yeong-Bae Lee1, Kee Hyung Park1, Jae-Hyeok Heo5, Cindy W Yoon6, Jae Myeong Kang7, Jaelim Cho8, Nobuyuki Okamura9, Shozo Furumoto10, Kazuhiko Yanai9,10, Duk L Na11,12, Tatsuo Ido3, Victor L Villemagne13,14, Young Noh1,15. 1. Departments of Neurology. 2. Department of Neuroscience, College of Medicine. 3. Neuroscience Research Institute. 4. Department of Neurology, Seoul National University Hospital. 5. Department of Neurology, Seoul Medical Center. 6. Department of Neurology, Inha University School of Medicine, Incheon. 7. Psychiatry. 8. Occupational and Environmental Medicine, Gachon University Gil Medical Center. 9. Department of Pharmacology, Tohoku Medical and Pharmaceutical University. 10. Cyclotron and Radioisotope Center, Tohoku University, Sendai, Japan. 11. Department of Neurology, Samsung Medical Center, Sungkyunkwan University School of Medicine. 12. Neuroscience Center, Samsung Medical Center, Seoul, Republic of Korea. 13. Department of Molecular Imaging and Therapy, Centre for PET, Austin Health. 14. The Florey Institute of Neuroscience and Mental Health, the University of Melbourne, Melbourne, Vic., Australia. 15. Department of Health Science and Technology, GAIHST, Gachon University.
Abstract
BACKGROUND: Semantic variant primary progressive aphasia (svPPA) has been associated with a variety of proteinopathies, mainly transactive response DNA-binding protein, but also with tau and β-amyloid. Recently selective tau tracers for positron emission tomography (PET) have been developed to determine the presence of cerebral tau deposits in vivo. Here, we investigated the topographical distribution of THK5351 in svPPA patients. MATERIALS AND METHODS: Five svPPA patients, 14 Alzheimer's disease patients, and 15 age-matched normal controls underwent [F]-THK5351 PET scans, magnetic resonance imaging, and detailed neuropsychological tests. [F]-fluorodeoxyglucose PET was obtained in 3 svPPA patients, whereas the remaining 2 underwent amyloid PET using [F]-flutemetamol. Tau distribution among the 3 groups was compared using regions of interest-based and voxel-based statistical analyses. RESULTS: In svPPA patients, [F]-THK5351 retention was elevated in the anteroinferior and lateral temporal cortices compared with the normal controls group (left>right), and in the left inferior and temporal polar region compared with Alzheimer's disease patients. [F]-THK5351 retention inversely correlated with glucose metabolism, whereas regional THK retention correlated with clinical severity. [F]-flutemetamol scans were negative for β-amyloid. CONCLUSIONS: These findings show that [F]-THK5351 retention may be detected in cortical regions correlating with svPPA pathology.
BACKGROUND: Semantic variant primary progressive aphasia (svPPA) has been associated with a variety of proteinopathies, mainly transactive response DNA-binding protein, but also with tau and β-amyloid. Recently selective tau tracers for positron emission tomography (PET) have been developed to determine the presence of cerebral tau deposits in vivo. Here, we investigated the topographical distribution of THK5351 in svPPA patients. MATERIALS AND METHODS: Five svPPA patients, 14 Alzheimer's diseasepatients, and 15 age-matched normal controls underwent [F]-THK5351 PET scans, magnetic resonance imaging, and detailed neuropsychological tests. [F]-fluorodeoxyglucose PET was obtained in 3 svPPA patients, whereas the remaining 2 underwent amyloid PET using [F]-flutemetamol. Tau distribution among the 3 groups was compared using regions of interest-based and voxel-based statistical analyses. RESULTS: In svPPA patients, [F]-THK5351 retention was elevated in the anteroinferior and lateral temporal cortices compared with the normal controls group (left>right), and in the left inferior and temporal polar region compared with Alzheimer's diseasepatients. [F]-THK5351 retention inversely correlated with glucose metabolism, whereas regional THK retention correlated with clinical severity. [F]-flutemetamol scans were negative for β-amyloid. CONCLUSIONS: These findings show that [F]-THK5351 retention may be detected in cortical regions correlating with svPPA pathology.
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