Alzheimer disease (AD), the most common form of dementia, is a heterogenous disorder with various pathobiological subtypes. In addition to the 4 major subtypes based on the distribution of tau pathology and brain atrophy (typical, limbic predominant, hippocampal sparing, and minimal atrophy [MA]), several other clinical variants showing distinct regional patterns of tau burden have been identified: nonamnestic, corticobasal syndromal, primary progressive aphasia, posterior cortical atrophy, behavioral/dysexecutive, and mild dementia variants. Among the subtypes, differences were found in age at onset, sex distribution, cognitive status, disease duration, APOE genotype, and biomarker levels. The patterns of key network destructions parallel the tau and atrophy patterns of the AD subgroups essentially. Interruption of key networks, in particular the default-mode network that is responsible for cognitive decline, is consistent in hetero­genous AD groups. AD pathology is often associated with co-pathologies: cerebrovascular lesions, Lewy pathology, and TDP-43 proteinopathies. These mixed pathologies essentially influence the clinical picture of AD and may accel­erate disease progression. Unraveling the heterogeneity among the AD spectrum entities is important for opening a window to pathogenic mechanisms affecting the brain and enabling precision medicine approaches as a basis for developing preventive and ultimately successful disease-modifying therapies for AD.
Dement Geriatr Cogn Disord

中文翻译：

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阿尔茨海默氏病的病理生物学亚型

阿尔茨海默病（AD）是痴呆症最常见的形式，是一种具有多种病理生物学亚型的异质性疾病。除了基于tau病理学分布和脑萎缩的4种主要亚型（典型，边缘性优势，海马保留和最小萎缩[MA]）外，还发现了其他几种显示tau负担的不同区域模式的临床变体：非遗忘性，皮质基底突综合征，原发性进行性失语症，后皮质萎缩，行为/功能失调和轻度痴呆。在亚型中，发现发病年龄，性别分布，认知状态，疾病持续时间，APOE基因型和生物标志物水平存在差异。关键网络破坏的模式基本上与AD子组的tau和萎缩模式平行。关键网络中断，尤其是负责认知能力下降的默认模式网络在异构AD组中是一致的。AD病理通常与以下共同病理相关：脑血管病变，路易氏病理和TDP-43蛋白病。这些混合病理本质上影响AD的临床情况，并可能加速疾病进展。揭示AD频谱实体之间的异质性对于打开影响大脑的致病机制的窗口，并使精密医学方法成为开发预防性和最终成功的AD治疗疾病的基础非常重要。和TDP-43蛋白病。这些混合病理本质上影响AD的临床情况，并可能加速疾病进展。揭示AD频谱实体之间的异质性对于打开影响大脑的致病机制的窗口，并使精密医学方法成为开发预防性和最终成功的AD治疗疾病的基础非常重要。和TDP-43蛋白病。这些混合病理本质上影响AD的临床情况，并可能加速疾病进展。揭示AD频谱实体之间的异质性对于打开影响大脑的致病机制的窗口，并使精密医学方法成为开发预防性和最终成功的AD治疗疾病的基础非常重要。
Dement Geriatr Cogn Disord