Jellinger K A
Ludwig Boltzmann Institute of Clinical Neurobiology, Wien, Austria.
J Neural Transm Suppl. 1998;53:97-118. doi: 10.1007/978-3-7091-6467-9_9.
The unequivocal diagnosis of Alzheimer disease (AD) rests on histopathological evidence at brain autopsy or biopsy. Although the histological features of AD are well known, defining criteria for the morphological diagnosis of AD is difficult due to the phenotypical heterogeneity of the disease, absence of specific markers, and overlap of AD pathology with that observed in non-demented elderly individuals. This gray zone between normal to pathological aging and full-fledged AD represents an important diagnostic problem and should be overcome by better standardized criteria that will allow to minimize interrater and interlaboratory variability in the diagnosis of AD. Current criteria for the neuropathological diagnosis of AD are based on age-related (semi)quantitative assessment of "senile" plaques (NIA criteria), neuritic plaques (CERAD), plaques and neurofibrillary tangles in neocortex and hippocampus (Tierney et al., 1988), and staging of hierarchic spreading of neuritic AD changes in particular, neurofibrillary tangles (Braak and Braak, 1991). All these algorithms have some weaknesses and do not recognize the various subtypes of AD. Multivariant analysis of an autopsy series of elderly subjects revealed significant correlations between psychostatus assessed by the Mini-Mental State and both the CERAD criteria and Braak staging. Although the role of plaques and tangles in the pathogenesis of AD and their relationship to both neuronal loss and dementia remain to be elucidated, clinicopathological studies have shown that both lesions, if present in sufficient numbers, particularly in the neocortex, are considered the best correlates for AD related dementia. Recent consensus recommendations of the NIA- and Reagan Institute Working Group for the morphological diagnosis of AD consider AD as a heterogenous clinicopathological entity. After exclusion of other causes of dementia, the likelihood that AD accounts for dementia is considered high, intermediate or low according to the frequency of neuritic AD lesions with regard to both the CERAD criteria and Braak staging. The evaluation of small autopsy series according to these criteria demonstrated their easy and rapid application in AD and non-demented subjects, with much less reliability for other dementing disorders.
阿尔茨海默病（AD）的确切诊断依赖于脑尸检或活检的组织病理学证据。尽管AD的组织学特征广为人知，但由于该疾病的表型异质性、缺乏特异性标志物以及AD病理学与非痴呆老年人中观察到的病理学存在重叠，因此难以确定AD形态学诊断的标准。正常衰老到病理性衰老以及典型AD之间的这个灰色地带代表了一个重要的诊断问题，应该通过更好的标准化标准来克服，这些标准将有助于最大限度地减少AD诊断中评估者之间和实验室之间的变异性。目前AD神经病理学诊断的标准基于对“老年”斑的年龄相关（半）定量评估（NIA标准）、神经炎斑（CERAD）、新皮质和海马中的斑和神经原纤维缠结（Tierney等人，1988年），特别是神经炎AD变化（尤其是神经原纤维缠结）的分级扩散分期（Braak和Braak，1991年）。所有这些算法都有一些弱点，并且无法识别AD的各种亚型。对老年受试者尸检系列的多变量分析显示，简易精神状态检查评估的心理状态与CERAD标准和Braak分期之间存在显著相关性。尽管斑和缠结在AD发病机制中的作用及其与神经元丢失和痴呆的关系仍有待阐明，但临床病理学研究表明，如果这两种病变数量足够，特别是在新皮质中，则被认为是AD相关痴呆的最佳相关因素。美国国立衰老研究所（NIA）和里根研究所工作组最近关于AD形态学诊断的共识建议认为AD是一种异质性临床病理实体。在排除其他痴呆原因后，根据CERAD标准和Braak分期，AD导致痴呆的可能性被认为是高、中或低。根据这些标准对小型尸检系列进行评估表明，它们在AD和非痴呆受试者中易于快速应用，但对其他痴呆性疾病的可靠性要低得多。
