Tau-PET imaging in Progressive Supranuclear Palsy and relationship with biomarkers and clinical markers

IF 11.1 1区医学 Q1 CLINICAL NEUROLOGY Alzheimer's & Dementia Pub Date : 2025-01-09 DOI:10.1002/alz.093950

Roxane Dilcher, Charles B Malpas, Terence J O'Brien, Lucy Vivash

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Abstract

Background

Identifying biomarkers for primary tau pathologies like Progressive Supranuclear Palsy (PSP) is crucial for diagnosis and treatment development. The novel positron emission tomography (PET) radiotracer 18F-PI-2620 shows promise in detecting tau protein in PSP and this study investigates its correlation with clinical markers.

Methods

We conducted a cross-sectional analysis on 20 patients with clinically diagnosed probable PSP (Richardson’s Syndrome), who underwent T1-weighted MRI, lumbar puncture, blood testing, and 0-60 min dynamic 18F-PI-2620 PET scanning. Binding potential (BD) and Standardized uptake value ratios (SUVr) were generated for regions of interest. Clinical assessments included the Digit Span Memory task, Hayling, Stroop, Trail Making Test, NIH toolbox subtasks, the BRIEF-A, and the PSP-RS. Voxel-wise and region-based multiple regression analyses were employed to examine relationship between PET metrics and clinical markers using FSL, SPM, and R software.

Results

Preliminary results revealed a significant negative correlation between basal ganglia tau uptake and the Digit Span Reverse task or the BRIEF-A (voxel-wise, SUVr: p<0.01; BD: p<0.05). Region-based analyses (SUVr) showed basal ganglia tau uptake significantly correlated with impairments in the Digit Span Forward and Reverse task (p<0.01), working memory subtask of the NIH (p<0.05), and the BRIEF-A (‘Never’-scores, p<0.05). Significant interaction effects (p<0.05) showed that these associations were predominantly localized in the basal ganglia as compared to frontal or occipital regions. Additionally, basal ganglia atrophy was negatively associated with tau uptake (SUVr) in the basal ganglia and brainstem. Ongoing analysis explores associations with CSF/blood biomarkers (GFAP/NfL/tau).

Conclusions

Our findings highlight the potential of 18F-PI-2620 as an in-vivo tau biomarker in PSP diagnosis, demonstrating significant links between tau uptake in the basal ganglia, brain atrophy, executive dysfunction, and disease severity. These insights could drive the development of new biomarkers, advancing future clinical trial prospects.

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进行性核上性麻痹的Tau-PET显像及其与生物标志物和临床标志物的关系

背景：确定原发性tau蛋白病变如进行性核上性麻痹（PSP）的生物标志物对诊断和治疗发展至关重要。新型正电子发射断层扫描（PET）示踪剂18F-PI-2620有望检测PSP中的tau蛋白，本研究探讨了其与临床标志物的相关性。方法对20例临床诊断为疑似PSP（理查德森综合征）的患者进行横断面分析，这些患者接受了t1加权MRI、腰椎穿刺、血液检查和0-60分钟动态18F-PI-2620 PET扫描。对感兴趣的区域产生结合电位（BD）和标准化摄取值比（SUVr）。临床评估包括数字广度记忆任务、Hayling、Stroop、Trail Making Test、NIH工具箱子任务、BRIEF-A和PSP-RS。使用FSL、SPM和R软件，采用体素和基于区域的多元回归分析来检查PET指标与临床标志物之间的关系。结果初步结果显示，基底节区tau摄取与数字跨度反向任务或BRIEF-A呈显著负相关(体素方向，SUVr: p<0.01；双相障碍:术;0.05)。基于区域的分析（SUVr）显示，基底神经节tau摄取与数字跨径正向和反向任务（p<0.01）、NIH工作记忆子任务（p<0.05）和BRIEF-A（“Never”得分，p<0.05）的损伤显著相关。显著的相互作用效应（p<0.05）表明，与额叶或枕叶区相比，这些关联主要集中在基底节区。此外，基底神经节萎缩与基底神经节和脑干的tau摄取（SUVr）呈负相关。正在进行的分析探索与CSF/血液生物标志物（GFAP/NfL/tau）的关联。我们的研究结果强调了18F-PI-2620作为PSP诊断中的体内tau生物标志物的潜力，证明了基底节区tau摄取、脑萎缩、执行功能障碍和疾病严重程度之间的显著联系。这些见解可以推动新的生物标志物的发展，推进未来的临床试验前景。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Alzheimer's & Dementia 医学-临床神经学

CiteScore

14.50

自引率

5.00%

发文量

299

审稿时长

3 months

期刊介绍： Alzheimer's & Dementia is a peer-reviewed journal that aims to bridge knowledge gaps in dementia research by covering the entire spectrum, from basic science to clinical trials to social and behavioral investigations. It provides a platform for rapid communication of new findings and ideas, optimal translation of research into practical applications, increasing knowledge across diverse disciplines for early detection, diagnosis, and intervention, and identifying promising new research directions. In July 2008, Alzheimer's & Dementia was accepted for indexing by MEDLINE, recognizing its scientific merit and contribution to Alzheimer's research.