Jellinger K A, Bancher C
Ludwig Boltzmann Institute of Clinical Neurobiology, Lainz-Hospital, Vienna, Austria.
Neurobiol Aging. 1997 Jul-Aug;18(4 Suppl):S55-65. doi: 10.1016/s0197-4580(97)00071-7.
Defining criteria for the postmortem diagnosis of Alzheimer's disease (AD) has proven difficult due to the phenotypical heterogeneity of the disease, the absence of a specific disease marker and an overlap of AD neuropathology with that observed in a number of nondemented aged individuals. Even though the role of plaques and tangles in the pathogenesis of AD remains undetermined, a host of clinicopathological correlative studies have shown that both lesions, if present in sufficient numbers-particularly in the neocortex-are still to be considered the best morphological signposts for the disease. All currently used criteria for the neuropathologic diagnosis of AD have some weaknesses and need to be reestablished and revalidated. Multivariant analysis in a personal autopsy series of elderly subjects revealed significant correlations between psychostatus and both the CERAD criteria and Braak staging of neuritic Alzheimer-type lesions, and less concordance with the National Institutes of Aging and Tierney criteria. We propose a set of histopathologic diagnostic criteria for both definite and preclinical AD that rely on various constellations of both different types of plaques, except diffuse amyloid deposits, and neurofibrillary tangles, in allocortical and isocortical areas considering their topographic pattern. This set of criteria encompasses phenotypic variations of the pathology and takes into account the chronic, progressive course of AD. It allows the detection of preclinical disease in subjects in whom dementia is not reported and includes those cases in the morphological gray zone between "normal" aging and full-fledged AD that practicing neuropathologists consider the most problematic. The set of criteria includes guidelines concerning tissue sampling and processing, and standardized staining methods that should allow neurologists to minimize interrater and interlaboratory variability in the assessment of morphologic lesions and the diagnosis of AD.
由于阿尔茨海默病（AD）的表型异质性、缺乏特异性疾病标志物以及AD神经病理学与许多非痴呆老年人中观察到的神经病理学存在重叠，因此确定AD的尸检诊断标准一直很困难。尽管斑块和缠结在AD发病机制中的作用尚未确定，但大量临床病理相关性研究表明，如果这两种病变数量足够多——尤其是在新皮质中——它们仍被认为是该疾病最佳的形态学标志。目前所有用于AD神经病理学诊断的标准都存在一些弱点，需要重新建立和验证。对一组老年受试者的个人尸检系列进行多变量分析发现，心理状态与CERAD标准和神经炎性阿尔茨海默型病变的Braak分期之间存在显著相关性，与美国国立衰老研究所和Tierney标准的一致性较低。我们提出了一套针对明确和临床前期AD的组织病理学诊断标准，该标准依赖于除弥漫性淀粉样沉积物之外的不同类型斑块以及神经原纤维缠结在allocortical和isocortical区域的各种组合，并考虑它们的地形模式。这组标准涵盖了病理学的表型变异，并考虑到了AD的慢性、进行性病程。它能够在未报告痴呆的受试者中检测到临床前期疾病，包括那些处于“正常”衰老和完全成熟的AD之间形态学灰色地带的病例，而执业神经病理学家认为这些病例最具问题。这组标准包括有关组织采样和处理的指南，以及标准化染色方法，这些应能使神经学家在评估形态学病变和诊断AD时尽量减少评分者间和实验室间的变异性。
