Breakthroughs in the development of highly accurate fluid and neuroimaging biomarkers have catalysed the conceptual transformation of Alzheimer disease (AD) from the traditional clinical symptom-based definition to a clinical–biological construct along a temporal continuum. The AT(N) system is a symptom-agnostic classification scheme that categorizes individuals using biomarkers that chart core AD pathophysiological features, namely the amyloid-β (Aβ) pathway (A), tau-mediated pathophysiology (T) and neurodegeneration (N). This biomarker matrix is now expanding towards an ATX(N) system, where X represents novel candidate biomarkers for additional pathophysiological mechanisms such as neuroimmune dysregulation, synaptic dysfunction and blood–brain barrier alterations. In this Perspective, we describe the conceptual framework and clinical importance of the existing AT(N) system and the evolving ATX(N) system. We provide a state-of-the-art summary of the potential contexts of use of these systems in AD clinical trials and future clinical practice. We also discuss current challenges related to the validation, standardization and qualification process and provide an outlook on the real-world application of the AT(N) system.

高精度流体和神经影像学生物标志物开发的突破促进了阿尔茨海默病 (AD) 从传统的基于临床症状的定义到时间连续体的临床-生物学结构的概念转变。AT(N) 系统是一种与症状无关的分类方案，它使用描绘核心 AD 病理生理特征的生物标志物对个体进行分类，即淀粉样蛋白-β (Aβ) 通路 (A)、tau 介导的病理生理学 (T) 和神经变性 (N) . 该生物标志物矩阵现在正在向 ATX(N) 系统扩展，其中 X 代表新的候选生物标志物，用于其他病理生理机制，例如神经免疫失调、突触功能障碍和血脑屏障改变。在这个观点中，我们描述了现有 AT(N) 系统和不断发展的 ATX(N) 系统的概念框架和临床重要性。我们提供了在 AD 临床试验和未来临床实践中使用这些系统的潜在背景的最先进的总结。我们还讨论了与验证、标准化和鉴定过程相关的当前挑战，并展望了 AT(N) 系统的实际应用。