Bancher C, Jellinger K, Lassmann H, Fischer P, Leblhuber F
Ludwig Boltzmann Institute of Clinical Neurobiology, Vienna, Austria.
Eur Arch Psychiatry Clin Neurosci. 1996;246(3):137-46. doi: 10.1007/BF02189115.
Quantitative clinicopathological correlation studies are one way to address the question of the relevance of morphological abnormalities in Alzheimer's dementia (AD). This paper summarizes results of the Vienna Longitudinal Study on Dementia obtained during the past few years and presents a critical discussion on the relevance of clinicopathological correlation studies for the pathogenesis of AD. Plotting of psychometric test scores against the numbers of plaques, tangles and neuropil threads in various cortical areas shows that significant correlations are due primarily to very high lesion counts in severely demented patients. These data indicate that neocortical neurofibrillary pathology can be considered an end-stage marker in the pathology of AD. On the other hand, the topographical staging of neuritic Alzheimer changes proposed by Braak and Braak (1991) appears to be a better reflection of the progression of the degenerative process than numerical lesion counts; there is a linear correlation between the Braak stages and Mini-Mental State scores in 122 aged individuals. Significant correlations are further obtained between the severity of dementia and the levels of a number of synaptic proteins including synaptophysin and the chromogranins. Taken together, our data suggest that none of the classical AD lesions, plaques and tangles, play a central role in the pathogenesis of dementia, a fact that is supported by a molecular biological study showing that there is no close relationship between these lesions and the neurons undergoing degeneration in AD. Whereas neuritic pathology is a useful histopathological marker for the diagnosis and staging of AD, the major correlate of cognitive deficits is the loss of corticocortical and subcorticocortical connections reflected by a depletion of synapses. This pathology may be induced by a mismetabolism of the beta-amyloid precursor proteins or their interaction with cytoskeletal proteins related to neuronal degeneration.
定量临床病理相关性研究是解决阿尔茨海默病（AD）形态学异常相关性问题的一种方法。本文总结了过去几年维也纳痴呆纵向研究的结果，并对临床病理相关性研究在AD发病机制中的相关性进行了批判性讨论。将心理测量测试分数与不同皮质区域的斑块、缠结和神经毡丝数量进行绘图显示，显著相关性主要归因于重度痴呆患者的病变计数非常高。这些数据表明，新皮质神经原纤维病理可被视为AD病理中的终末期标志物。另一方面，Braak和Braak（199）提出的神经炎型阿尔茨海默病变化的拓扑分期似乎比病变数量计数更能反映退行性过程的进展；在122名老年人中，Braak分期与简易精神状态评分之间存在线性相关性。痴呆严重程度与包括突触素和嗜铬粒蛋白在内的多种突触蛋白水平之间进一步获得了显著相关性。综上所述，我们的数据表明，经典的AD病变，即斑块和缠结，在痴呆发病机制中均不发挥核心作用，这一事实得到了一项分子生物学研究的支持，该研究表明这些病变与AD中发生退变的神经元之间没有密切关系。虽然神经炎病理是AD诊断和分期的有用组织病理学标志物，但认知缺陷的主要相关因素是突触耗竭所反映的皮质皮质和皮质下皮质连接的丧失。这种病理可能是由β-淀粉样前体蛋白的代谢异常或它们与神经元退变相关的细胞骨架蛋白的相互作用所诱导的。
