阿尔茨海默病中的白质异常：对病理生理学、诊断和治疗的启示
White matter abnormalities in Alzheimer's disease: Implications for pathophysiology, diagnosis, and treatment.
摘要(中文译文)
白质（WM）异常已成为阿尔茨海默病（AD）发病机制中的关键要素，其地位已从过去被认为是被动后果转变为疾病进展的主动调控者。值得注意的是，通过扩散张量成像等先进神经影像技术可在早期检测到的白质微结构改变，往往先于明显的灰质萎缩和认知功能下降，凸显其作为AD病理级联反应中早期启动事件的潜力。白质病理的起源是多因素的，涉及β-淀粉样蛋白（Aβ）与tau聚集、能量代谢障碍、神经炎症、血管功能障碍及细胞衰老之间复杂的相互作用。重要的是，我们强调一种范式转变的视角：白质变性不仅是下游结果，更是AD发病机制的关键contributor，能够加速蛋白质聚集、放大神经炎症并损害神经可塑性。鉴于其早期表现及与症状发作的密切关联，白质完整性已成为早期AD检测和进展监测的敏感且可靠的生物标志物。超越诊断层面，对白质病理生理学认识的不断深入开辟了以髓鞘再生和白质保护为目标的新型治疗干预前沿。尽管转化挑战依然存在，靶向白质完整性代表了开发能够延缓疾病进展并改善AD患者临床结局的疾病修饰疗法的关键途径。
Abstract
White matter (WM) abnormalities have emerged as a critical element in Alzheimer's disease (AD) pathogenesis, shifting from their former status as a passive consequence to an active regulator of disease progression. Notably, microstructural WM alterations, detectable early via advanced neuroimaging techniques such as diffusion tensor imaging, frequently precede overt gray matter atrophy and cognitive decline, highlighting their potential as early initiating events in the AD pathological cascade. The origins of WM pathology are multifactorial, involving a complex interplay among β-amyloid (Aβ) and tau aggregation, energy dysmetabolism, neuroinflammation, vascular dysfunction, and cellular senescence. Importantly, we emphasize a paradigm-shifting perspective: WM degeneration acts not merely as a downstream outcome but as a key contributor of AD pathogenesis, capable of accelerating protein aggregation, amplifying neuroinflammation, and compromising neural plasticity. Given its early manifestation and close association with symptom onset, WM integrity has emerged as a sensitive and reliable biomarker for early AD detection and progression monitoring. Moving beyond diagnostics, the growing understanding of WM pathophysiology has unveiled a new frontier of therapeutic interventions aimed at myelin regeneration and WM protection. Despite persisting translational challenges, targeting WM integrity represents a pivotal avenue for developing disease-modifying therapies capable of slowing disease progression and improving clinical outcomes in patients with AD.
如何引用
AMA
Zhichun Chen, Kangyan Yang, Feifei Lin, Weiting Tang, Yuxuan Shi, Sizhe Zhou, et al. White matter abnormalities in Alzheimer's disease: Implications for pathophysiology, diagnosis, and treatment.. Ageing research reviews. 2026; doi:10.1016/j.arr.2026.103229.
APA
Zhichun Chen, Kangyan Yang, Feifei Lin, Weiting Tang, Yuxuan Shi, Sizhe Zhou, et al (2026). White matter abnormalities in Alzheimer's disease: Implications for pathophysiology, diagnosis, and treatment.. Ageing research reviews. https://doi.org/10.1016/j.arr.2026.103229
GB/T 7714
Zhichun Chen, Kangyan Yang, Feifei Lin, Weiting Tang, Yuxuan Shi, Sizhe Zhou, et al. White matter abnormalities in Alzheimer's disease: Implications for pathophysiology, diagnosis, and treatment.[J]. Ageing research reviews, 2026 doi:10.1016/j.arr.2026.103229.
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