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 [F]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).
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http://dx.doi.org/10.1016/j.ebiom.2023.104835 | DOI Listing |
CNS Drugs
January 2025
Department of Cardiology, Second Affiliated Hospital of Dalian Medical University, Dalian, China.
Background: Early neurological deterioration (END) is associated with a poor prognosis in acute ischemic stroke (AIS). Effectively lowering low-density lipoprotein cholesterol (LDL-C) can improve the stability of atherosclerotic plaque and reduce post-stroke inflammation, which may be an effective means to lower the incidence of END. The objective of this study was to determine the preventive effects of evolocumab on END in patients with non-cardiogenic AIS.
View Article and Find Full Text PDFSci Rep
January 2025
Gynecology Department, Affiliated Hospital of Nanjing University of Chinese Medicine, Nanjing, 210029, China.
The presence of high-risk human papillomavirus (HR-HPV) contributes to the development of cervical lesions and cervical cancer. Recent studies suggest that an imbalance in the cervicovaginal microbiota might be a factor in the persistence of HR-HPV infections. In this study, we collected 156 cervicovaginal fluid (CVF) of women with HR-HPV infection, which were divided into three groups (negative for intraepithelial lesions = 78, low/high-grade squamous intraepithelial lesions = 52/26).
View Article and Find Full Text PDFJ Mol Med (Berl)
January 2025
Cardiovascular Surgery Department of The First Affiliated Hospital of Harbin Medical University, and Pharmacology Department of Pharmacy College of Harbin Medical University, Harbin, 150081, China.
Myocardial ischemia/reperfusion (IR) injury is a common adverse event in the clinical treatment of myocardial ischemic disease. Autosis is a form of cell death that occurs when autophagy is excessive in cells, and it has been associated with cardiac IR damage. This study aimed to investigate the regulatory mechanism of circRNA CDR1AS on autosis in cardiomyocytes under IR.
View Article and Find Full Text PDFMol Cell Biochem
January 2025
Department of Urology, Guizhou Provincial People's Hospital, Guiyang, 550002, China.
Selenium, an essential trace mineral for health, has seen a rise in clinical trials over the past nearly 5 decades. Our aim here is to provide a comprehensive and concise overview of selenium clinical trials from 1976 to 2023. Overall, the evolution of selenium clinical trials over 48 years has advanced through phases of emergence, prosperity, and either stability or transition.
View Article and Find Full Text PDFWorld J Urol
January 2025
Department of Urology, Peking University People's Hospital, Beijing, 100044, China.
Purpose: This study aims to elucidate the role of pituitary adenylate cyclase-activating polypeptide (PACAP) in Hunner-type Interstitial Cystitis (HIC) and evaluate its potential as a therapeutic target.
Methods: Bladder tissue samples were obtained from HIC patients and normal bladder tissue from bladder cancer patients. PACAP expression was assessed through immunohistochemistry.
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