Imaging microtubule dynamics: A new frontier in biomarker development for neurodegenerative diseases

IF 11.1 1区医学 Q1 CLINICAL NEUROLOGY

Alzheimer's & Dementia Pub Date : 2025-09-23 DOI:10.1002/alz.70670

Naresh Damuka, Samuel N. Lockhart, Kiran K. Solingapuram Sai

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引用次数: 0

Abstract

Microtubules (MTs) are essential components of the neuronal cytoskeleton, playing key roles in intracellular transport, synaptic function, and overall neuronal integrity. Although MT dynamics and MT-binding agents have been studied extensively, their potential as biomarkers in neurodegenerative diseases has received limited attention. Emerging evidence suggests that MT destabilization is one of the earliest pathological events in Alzheimer's disease, Parkinson's disease, and other related disorders. This review highlights MT dysregulation as a promising marker of early neurodegenerative changes and discusses recent advances in imaging tools, particularly positron emission tomography (PET), that enable in vivo visualization of MT dynamics. We focus on the development and application of novel MT-targeting PET radiotracers, such as [¹¹C]MPC-6827, which demonstrate high specificity for destabilized MTs and excellent brain uptake. To our knowledge, this is the first comprehensive review emphasizing MT alterations as a translational imaging biomarker, offering a new perspective in the early detection and monitoring of neurodegenerative diseases.

Highlights

Microtubule (MT) instability is an early and underrecognized event in neurodegenerative disease pathogenesis and may precede classical hallmarks of Alzheimer's disease pathology.
MT dysregulation holds promise as a novel diagnostic biomarker, offering new opportunities for early detection and disease monitoring in Alzheimer's disease, Parkinson's disease, and related disorders.
Recent advances in MT-targeted positron emission tomography imaging, particularly with [¹¹C]MPC-6827, enable non-invasive, in vivo visualization of MT dynamics with high specificity and brain penetration.
Cross-species validation of MT imaging, from rodent models to non-human primates and humans, demonstrates strong translational potential, supporting its future clinical application.
Integration of MT imaging with established amyloid, tau, and neuroinflammation markers enhances diagnostic precision, supports early intervention strategies, and enables more personalized approaches to neurodegenerative disease care.

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成像微管动力学：神经退行性疾病生物标志物开发的新前沿

微管（MTs）是神经元细胞骨架的重要组成部分，在细胞内运输、突触功能和整体神经元完整性中发挥关键作用。尽管MT动力学和MT结合剂已被广泛研究，但它们作为神经退行性疾病生物标志物的潜力却受到有限的关注。新出现的证据表明MT不稳定是阿尔茨海默病、帕金森病和其他相关疾病的最早病理事件之一。这篇综述强调了MT失调是早期神经退行性改变的一个有希望的标志，并讨论了成像工具的最新进展，特别是正电子发射断层扫描（PET），它可以实现MT动态的体内可视化。我们专注于新型靶向MT - PET放射性示踪剂的开发和应用，如[11C]MPC - 6827，它对不稳定的MT具有高特异性和良好的脑摄取。据我们所知，这是第一篇强调MT改变作为翻译成像生物标志物的综合综述，为神经退行性疾病的早期检测和监测提供了新的视角。微管（MT）不稳定性是神经退行性疾病发病机制的早期和未被充分认识的事件，可能先于阿尔茨海默病病理的经典标志。MT失调有望作为一种新的诊断生物标志物，为阿尔茨海默病、帕金森病和相关疾病的早期检测和疾病监测提供新的机会。最近，针对MT的正电子发射断层成像技术取得了进展，特别是使用[11C]MPC‐6827，可以实现MT动态的非侵入性、高特异性和脑穿透性的活体可视化。跨物种验证的MT成像，从啮齿动物模型到非人类灵长类动物和人类，显示出强大的转化潜力，支持其未来的临床应用。将MT成像与已建立的淀粉样蛋白、tau蛋白和神经炎症标志物相结合，可以提高诊断精度，支持早期干预策略，并使神经退行性疾病的治疗更加个性化。

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.