Uncovering distinct progression patterns of tau deposition in progressive supranuclear palsy using [18F]Florzolotau PET imaging and subtype/stage inference algorithmResearch in context
Jimin Hong,
Jiaying Lu,
Fengtao Liu,
Min Wang,
Xinyi Li,
Christoph Clement,
Leonor Lopes,
Matthias Brendel,
Axel Rominger,
Tzu-Chen Yen,
Yihui Guan,
Mei Tian,
Jian Wang,
Chuantao Zuo,
Kuangyu Shi,
Jian Wang,
Fengtao Liu,
Chuantao Zuo,
Jianjun Wu,
Yimin Sun,
Ping Wu,
Yilin Tang,
Jue Zhao,
Bin Wu,
Bo Shen,
Jiaying Lu,
Xinyue Zhou,
Xinyi Li,
Huiwei Zhang,
Jingjie Ge,
Minjia Chen,
Zizhao Ju
Affiliations
Jimin Hong
Department of Nuclear Medicine, Inselspital, University of Bern, Bern, Switzerland; Graduate School for Cellular and Biomedical Sciences, University of Bern, Switzerland
Jiaying Lu
Department of Nuclear Medicine & PET Center, Huashan Hospital, Fudan University, Shanghai, China; Department of Nuclear Medicine, Inselspital, University of Bern, Bern, Switzerland; National Center for Neurological Disorders & National Clinical Research Center for Aging and Medicine, State Key Laboratory of Medical Neurobiology, Huashan Hospital, Fudan University, Shanghai, China
Fengtao Liu
National Center for Neurological Disorders & National Clinical Research Center for Aging and Medicine, State Key Laboratory of Medical Neurobiology, Huashan Hospital, Fudan University, Shanghai, China; Department of Neurology, Huashan Hospital, Fudan University, Shanghai, China
Min Wang
Institute of Biomedical Engineering, School of Life Science, Shanghai University, Shanghai, China; Department of Informatics, Technical University of Munich, Munich, Germany
Xinyi Li
National Center for Neurological Disorders & National Clinical Research Center for Aging and Medicine, State Key Laboratory of Medical Neurobiology, Huashan Hospital, Fudan University, Shanghai, China; Department of Neurology, Huashan Hospital, Fudan University, Shanghai, China
Christoph Clement
Department of Nuclear Medicine, Inselspital, University of Bern, Bern, Switzerland; Graduate School for Cellular and Biomedical Sciences, University of Bern, Switzerland
Leonor Lopes
Department of Nuclear Medicine, Inselspital, University of Bern, Bern, Switzerland; Graduate School for Cellular and Biomedical Sciences, University of Bern, Switzerland
Matthias Brendel
Department of Nuclear Medicine, University of Munich, Munich, Germany; German Center for Neurodegenerative Diseases (DZNE), Munich, Germany; Munich Cluster for Systems Neurology (SyNergy), Munich, Germany
Axel Rominger
Department of Nuclear Medicine, Inselspital, University of Bern, Bern, Switzerland
Tzu-Chen Yen
APRINOIA Therapeutics Co., Ltd, Suzhou, China
Yihui Guan
Department of Nuclear Medicine & PET Center, Huashan Hospital, Fudan University, Shanghai, China; National Center for Neurological Disorders & National Clinical Research Center for Aging and Medicine, State Key Laboratory of Medical Neurobiology, Huashan Hospital, Fudan University, Shanghai, China
Mei Tian
Department of Nuclear Medicine & PET Center, Huashan Hospital, Fudan University, Shanghai, China; Human Phenome Institute, Fudan University, Shanghai, China; International Human Phenome Institutes (Shanghai), Shanghai, China
Jian Wang
National Center for Neurological Disorders & National Clinical Research Center for Aging and Medicine, State Key Laboratory of Medical Neurobiology, Huashan Hospital, Fudan University, Shanghai, China; Department of Neurology, Huashan Hospital, Fudan University, Shanghai, China; Corresponding author. Department of Neurology, Huashan Hospital, Fudan University, Shanghai, China.
Chuantao Zuo
Department of Nuclear Medicine & PET Center, Huashan Hospital, Fudan University, Shanghai, China; National Center for Neurological Disorders & National Clinical Research Center for Aging and Medicine, State Key Laboratory of Medical Neurobiology, Huashan Hospital, Fudan University, Shanghai, China; Human Phenome Institute, Fudan University, Shanghai, China; Corresponding author. Department of Nuclear Medicine & PET Center, Huashan Hospital, Fudan University, Shanghai, China.
Kuangyu Shi
Department of Nuclear Medicine, Inselspital, University of Bern, Bern, Switzerland; Department of Informatics, Technical University of Munich, Munich, Germany
Summary: Background: Progressive supranuclear palsy (PSP) is a primary 4-repeat tauopathy with diverse clinical phenotypes. Previous post-mortem studies examined tau deposition sequences in PSP, but in vivo scrutiny is lacking. Methods: We conducted [18F]Florzolotau tau positron emission tomography (PET) scans on 148 patients who were clinically diagnosed with PSP and 20 healthy controls. We employed the Subtype and Stage Inference (SuStaIn) algorithm to identify PSP subtype/stage and related tau patterns, comparing clinical features across subtypes and assessing PSP stage-clinical severity association. We also evaluated functional connectivity differences among subtypes through resting-state functional magnetic resonance imaging. Findings: We identified two distinct subtypes of PSP: Subtype1 and Subtype2. Subtype1 typically exhibits a sequential progression of the disease, starting from subcortical and gradually moving to cortical regions. Conversely, Subtype2 is characterized by an early, simultaneous onset in both regions. Interestingly, once the disease is initiated, Subtype1 tends to spread more rapidly within each region compared to Subtype2. Individuals categorized as Subtype2 are generally older and exhibit less severe dysfunctions in areas such as cognition, bulbar, limb motor, and general motor functions compared to those with Subtype1. Moreover, they have a more favorable prognosis in terms of limb motor function. We found significant correlations between several clinical variables and the identified PSP SuStaIn stages. Furthermore, Subtype2 displayed a remarkable reduction in functional connectivity compared to Subtype1. Interpretation: We present the evidence of distinct in vivo spatiotemporal tau trajectories in PSP. Our findings can contribute to precision medicine advancements for PSP. Funding: This work was supported by grants from the National Natural Science Foundation of China (number 82272039, 81971641, 82021002, and 92249302); Swiss National Science Foundation (number 188350); the STI2030-Major Project of China (number 2022ZD0211600); the Clinical Research Plan of Shanghai Hospital Development Center of China (number SHDC2020CR1038B); and the National Key R&D Program of China (number 2022YFC2009902, 2022YFC2009900), the China Scholarship Council (number 202006100181); the Deutsche Forschungsgemeinschaft (DFG) under Germany's Excellence Strategy within the framework of the Munich Cluster for Systems Neurology (EXC 2145 SyNergy, ID 390857198).
