The history of Alzheimer's disease (AD) started in 1907, but we needed to wait until the end of the century to identify the component of pathological hallmarks, genetic subtypes and to formulate the first pathogenic hypothesis. Thanks to biomarkers and new technologies, the concept of AD then rapidly changed from a static view of an amnestic dementia of the presenium to a biological entity that could be clinically manifested as normal cognition or dementia of different types. What is clearly emerging from studies is that AD is heterogeneous in each aspect, such as amyloid composition, tau distribution, relation between amyloid and tau, clinical symptoms, genetic background, and thus it is probably impossible to explain AD with a single pathological process. The scientific approach to AD suffers from chronological mismatches between clinical, pathological and technological data, causing difficulty in conceiving diagnostic gold standards and in creating models for drug discovery and screening. A recent mathematical computer-based approach offers the opportunity to study AD in real life and to provide a new point of view and the final missing pieces of the AD puzzle.

中文翻译：

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阿尔茨海默病的复杂性：一个不断演变的谜题

阿尔茨海默病 (AD) 的历史始于 1907 年，但我们需要等到本世纪末才能确定病理标志的组成部分、遗传亚型并制定第一个致病假说。多亏了生物标志物和新技术，AD 的概念随后迅速从对早老性遗忘性痴呆的静态观点转变为可以在临床上表现为正常认知或不同类型痴呆的生物实体。研究清楚地表明，AD在各个方面都是异质的，例如淀粉样蛋白组成、tau分布、淀粉样蛋白与tau的关系、临床症状、遗传背景，因此可能无法用单一的病理过程来解释AD。AD 的科学方法在临床、病理和技术数据，导致难以构思诊断金标准以及创建药物发现和筛选模型。最近的一种基于计算机的数学方法提供了在现实生活中研究 AD 的机会，并提供了一个新的观点和 AD 难题的最终缺失部分。