Department of Neuroscience, The Mayo Clinic Florida, 4500 San Pablo Road, Jacksonville, FL, 32224, USA.
Mol Neurodegener. 2019 Aug 2;14(1):32. doi: 10.1186/s13024-019-0333-5.
Alzheimer's disease is a progressive neurodegenerative disease most often associated with memory deficits and cognitive decline, although less common clinical presentations are increasingly recognized. The cardinal pathological features of the disease have been known for more than one hundred years, and today the presence of these amyloid plaques and neurofibrillary tangles are still required for a pathological diagnosis. Alzheimer's disease is the most common cause of dementia globally. There remain no effective treatment options for the great majority of patients, and the primary causes of the disease are unknown except in a small number of familial cases driven by genetic mutations. Confounding efforts to develop effective diagnostic tools and disease-modifying therapies is the realization that Alzheimer's disease is a mixed proteinopathy (amyloid and tau) frequently associated with other age-related processes such as cerebrovascular disease and Lewy body disease. Defining the relationships between and interdependence of various co-pathologies remains an active area of investigation. This review outlines etiologically-linked pathologic features of Alzheimer's disease, as well as those that are inevitable findings of uncertain significance, such as granulovacuolar degeneration and Hirano bodies. Other disease processes that are frequent, but not inevitable, are also discussed, including pathologic processes that can clinically mimic Alzheimer's disease. These include cerebrovascular disease, Lewy body disease, TDP-43 proteinopathies and argyrophilic grain disease. The purpose of this review is to provide an overview of Alzheimer's disease pathology, its defining pathologic substrates and the related pathologies that can affect diagnosis and treatment.
阿尔茨海默病是一种进行性神经退行性疾病，最常与记忆缺陷和认知能力下降有关，但越来越多的人认识到不太常见的临床表现。这种疾病的主要病理特征已经存在了一百多年，今天，这些淀粉样斑块和神经原纤维缠结仍然是病理诊断所必需的。阿尔茨海默病是全球最常见的痴呆症病因。除了少数由基因突变驱动的家族病例外，绝大多数患者仍然没有有效的治疗选择，而且除了少数家族病例外，这种疾病的主要病因仍不清楚。导致开发有效的诊断工具和疾病修饰疗法的努力受到阻碍的原因是，人们意识到阿尔茨海默病是一种混合性蛋白病（淀粉样蛋白和tau 蛋白），经常与其他与年龄相关的过程（如脑血管疾病和路易体疾病）相关。定义各种共病之间的关系和相互依存性仍然是一个活跃的研究领域。这篇综述概述了与阿尔茨海默病病因相关的病理特征，以及那些不可避免但意义不明的发现，如颗粒空泡变性和 Hirano 小体。还讨论了其他经常发生但并非不可避免的疾病过程，包括在临床上可能模仿阿尔茨海默病的病理过程。这些包括脑血管疾病、路易体疾病、TDP-43 蛋白病和嗜银颗粒病。本文综述的目的是提供阿尔茨海默病病理学概述，其定义性病理底物以及可能影响诊断和治疗的相关病理学。
