神经环路损伤及修复在阿尔茨海默病发病及康复中的作用及机制研究进展

The role and mechanisms of neural circuit damage and repair in the onset and recovery of Alzheimer's disease

  • 摘要: 阿尔茨海默病(AD)是一种以进行性认知衰退为核心的神经退行性疾病,其核心病理涉及多种神经环路的结构与功能障碍,但神经环路在AD发生与康复中的动态演变机制尚不明确。本文综述旨在系统阐述AD中关键神经环路(如海马-内嗅皮层环路、Papez环路等)的损伤机制,并重点探讨其修复与重塑的研究进展。文中不仅总结了Aβ/Tau病理与环路功能障碍的相互作用,更深入分析了神经环路异常早于典型病理沉积的潜在假说及其证据。此外,文章系统评估了多种基于环路的干预策略(如神经调控技术等)在AD治疗中的应用潜力与挑战,强调了靶向神经环路重塑的治疗新范式对于延缓疾病进程、促进功能康复的重要意义,为理解AD的环路机制和开发精准治疗策略提供理论依据。

     

    Abstract: Alzheimer's disease (AD) is characterized by progressive cognitive decline rooted in structural and functional impairment of neural circuits. The dynamic mechanisms governing circuit pathology and repair in AD remain elusive. In this article, the injury mechanisms within core AD circuits (e.g., hippocampo-entorhinal and Papez circuits) were systematically illustrated, highlighting the advances in their repair and reorganization. Beyond summarizing the Aβ/Tau pathology-circuit dysfunction interaction, the hypothesis that circuit abnormalities precede protein deposition was also critically examined. Furthermore, the potential and challenges of circuit-targeted interventions (e.g., neuromodulation, etc.) in the treatment of AD were evaluated. We advocate for a precision therapeutic paradigm focused on circuit remodeling to effectively slow disease progression and promote recovery. This work provides a theoretical framework for AD circuitopathy and guides the development of targeted therapies.

     

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