Clinicopathologic correlations in a large Alzheimer disease center autopsy cohort:: Neuritic plaques and neurofibrillary tangles "Do Count" when staging disease severity
Clinicopathologic correlations in a large Alzheimer disease center autopsy cohort:: Neuritic plaques and neurofibrillary tangles "Do Count" when staging disease severity
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DOI：
10.1097/nen.0b013e31815c5efb
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发表时间：
2007-12-01
影响因子：
3.2
通讯作者：
Markesbery, William R.
中科院分区：
文献类型：
--
作者：
Nelson, Peter T.;Jicha, Gregory A.;Markesbery, William R.
关于阿尔茨海默病（AD）中认知功能下降与经典组织病理学特征神经纤维素缠结（NFT）和“神经炎性”淀粉样斑块（INN）的关系尚不确定。这种不确定性加剧了对NFT和NP诊断重要性的怀疑，并导致关于AD发病机制假设的混乱。390名受试者接受纵向尸检前临床检查和尸检定量神经病理学评估作为一组来解决这个问题。对伴随脑部疾病的受试者进行独立分析，以更准确地评估不同病理对认知下降的贡献。超过60%的所有年龄组的患者有重要的非AD脑病变。然而，没有叠加脑部疾病的受试者显示AD型病理计数（NFT> NP）与死前简易精神状态检查评分之间有很强的相关性。所观察到的相关性在同皮质中比在异皮质中更强，并且在包括90岁以上的患者在内的各年龄组中保持。提出了一个理论模型，其中我们的结果被解释为支持AD发病机制的“淀粉样蛋白级联假说”。我们的数据显示，有许多重要的原因导致老年人的认知能力下降。然而，NFT和NP不应该被认为与AD的临床病理相关性无关。
There is uncertainty regarding the association of cognitive decline in Alzheimer disease (AD) with classic histopathologic features neurofibrillan tangles (NFTs) and ''neuritic'' amyloid plaques INN). This uncertainty fuels doubts about the diagnostic importance of NFTs and NPs and leads to confusion regarding hypotheses of AD pathogenesis. Three hundred ninety subjects who underwent longitudinal premortem clinical workup and postmortem quantitative neuropathologic assessment served as the group to address this issue. Subjects with concomitant brain disease(s) were analyzed independently to more accurately assess the contribution of distinct pathologies to cognitive decline. More than 60% of patients of all age groups had important non-AD brain pathologies. However, subjects without superimposed brain diseases showed strong correlations between AD-type pathology counts (NFTs > NPs) and premortem Mini-Mental State Examination scores. The observed correlation was stronger in isocortex than in allocortex and was maintained across age groups including patients older than 90 years. A theoretical model is proposed in which our results are interpreted to support the ''amyloid cascade hypothesis'' of AD pathogenesis. Our data show that there are many important contributory causes to cognitive decline in older persons. However, NFTs and NPs should not be dismissed as irrelevant in AD based on clinicopathologic correlation.