Nagy Z, Esiri M M, Jobst K A, Morris J H, King E M, McDonald B, Litchfield S, Smith A, Barnetson L, Smith A D
Department of Neuropathology, Radcliffe Infirmary NHS Trust, Oxford, UK.
Dementia. 1995 Jan-Feb;6(1):21-31. doi: 10.1159/000106918.
We have performed a quantitative analysis of the amyloid load (plaques), neuritic plaques and neurofibrillary tangles (NFT) in the frontal, temporal and parietal association cortices of autopsied brains from 49 prospectively evaluated patients with Alzheimer's disease (AD) diagnosed according to three sets of published pathological criteria. These patients had been assessed clinically with psychological testing of cognitive abilities within 6 months of death. Correlations were sought between severity of pathological change and cognitive status before death, duration of disease and age at death. Using Khachaturian and CERAD criteria highly positive correlations were obtained between the extent of cognitive deficit and the density of NFT in frontal and parietal lobes. The percentage area of cortex occupied by amyloid in the parietal lobe was correlated to the cognitive deficit only in the CERAD-diagnosed cases. The density of all amyloid plaques (AP) showed no correlation with the extent of cognitive deficit, but the densities of neuritic plaques did correlate with cognitive deficit. Both amyloid load and tangle densities were positively correlated with disease duration. All these correlations were reduced or absent in a subgroup of cases fulfilling the Tierney et al. A3 diagnostic criteria for AD. We found no pathological measure that correlated with the age of patients at death. Amyloid loads and NFT densities showed highly significant but selective positive correlations, the most striking being between temporal lobe NFT density and frontal and parietal lobe amyloid load and between temporal lobe NFT density and frontal and parietal lobe NFT densities. Correlations involving AP density as a measure of amyloid load were almost always less significant than those involving the percentage area of cortex occupied by amyloid, suggesting that the latter measures amyloid load more accurately. However, the highest correlations of NFT densities were with neuritic plaque densities. Overall this study highlights the relevance of neuritic changes (revealed by NFT and neuritic plaques) and the irrelevance of amyloid plaques to the dementia of AD.
我们对49例经前瞻性评估的阿尔茨海默病（AD）患者尸检大脑的额叶、颞叶和顶叶联合皮质中的淀粉样蛋白负荷（斑块）、神经炎性斑块和神经原纤维缠结（NFT）进行了定量分析。这些患者是根据三套已发表的病理标准诊断出来的。他们在死亡前6个月内接受了认知能力的心理测试临床评估。我们探寻了病理变化的严重程度与死亡前认知状态、疾病持续时间和死亡年龄之间的相关性。使用哈恰图良和CERAD标准，在额叶和顶叶中，认知缺陷程度与NFT密度之间获得了高度正相关。仅在CERAD诊断的病例中，顶叶中淀粉样蛋白占据的皮质百分比面积与认知缺陷相关。所有淀粉样蛋白斑块（AP）的密度与认知缺陷程度均无相关性，但神经炎性斑块的密度与认知缺陷相关。淀粉样蛋白负荷和缠结密度均与疾病持续时间呈正相关。在符合Tierney等人AD的A3诊断标准的病例亚组中，所有这些相关性均降低或不存在。我们未发现与患者死亡年龄相关的病理指标。淀粉样蛋白负荷和NFT密度显示出高度显著但具有选择性的正相关，最显著的是颞叶NFT密度与额叶和顶叶淀粉样蛋白负荷之间以及颞叶NFT密度与额叶和顶叶NFT密度之间。涉及AP密度作为淀粉样蛋白负荷指标的相关性几乎总是不如涉及淀粉样蛋白占据的皮质百分比面积的相关性显著，这表明后者能更准确地衡量淀粉样蛋白负荷。然而，NFT密度的最高相关性是与神经炎性斑块密度相关。总体而言，这项研究突出了神经炎性变化（由NFT和神经炎性斑块揭示）与AD痴呆中淀粉样蛋白斑块的无关性。
