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

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.