McKeel Daniel W, Price Joseph L, Miller J Philip, Grant Elizabeth A, Xiong Chengjie, Berg Leonard, Morris John C
Dept. of Pathology, Washington University School of Medicine, St. Louis, MO 63110, USA.
J Neuropathol Exp Neurol. 2004 Oct;63(10):1028-37. doi: 10.1093/jnen/63.10.1028.
Universally accepted neuropathologic criteria for differentiating Alzheimer disease (AD) from healthy brain aging do not exist. We tested the hypothesis that Bielschowsky silver stained total, cored, and neuritic senile plaques (TSPs, CSPs, and NSPs, respectively), rather than neurofibrillary tangles (NFTs), best discriminate between the 2 conditions using rigorously defined nondemented (n = 7) and AD (n = 35) subjects with no known co-morbidities. We compared lesions in 3 neocortical regions, in hippocampal CA1, and in entorhinal cortex in 19 men and 13 women between 74 and 86 years at death. The Clinical Dementia Rating (CDR) was used to assess degree of cognitive impairment within a year of demise. Neocortical TSP measures provided the highest correlation with expiration CDR: area under the curve (AUC) = 0.986 with 97.8% sensitivity at 90% specificity with an estimated cut-point of 6.0 TSP/ mm2. All SP measures yielded higher estimated AUC and sensitivity for 90% specificity compared to NFTs. Derived TSP cut-points applied to 149 persons with clinical AD regardless of their neuropathologic diagnosis yielded a sensitivity of 97% and specificity of 84% for TSPs in the 3 neocortical areas. Thus cut-points based on both diffuse and neuritic SP in neocortical regions distinguished nondemented and AD subjects with high sensitivity and specificity.
目前尚不存在被普遍接受的用于区分阿尔茨海默病（AD）与健康脑老化的神经病理学标准。我们检验了这样一种假设：与神经原纤维缠结（NFTs）相比， Bielschowsky银染色的总老年斑、核心老年斑和神经炎型老年斑（分别为TSPs、CSPs和NSPs）能最好地区分这两种情况。我们使用了严格定义的无已知合并症的非痴呆（n = 7）和AD（n = 35）受试者进行研究。我们比较了19名男性和13名女性（年龄在74至86岁之间）死亡时3个新皮质区域、海马CA1区和内嗅皮质中的病变情况。临床痴呆评定量表（CDR）用于评估死亡前一年内的认知障碍程度。新皮质TSP测量值与临终时的CDR相关性最高：曲线下面积（AUC）= 0.986，在90%特异性时灵敏度为97.8%，估计切点为6.0个TSP/mm2。与NFTs相比，所有SP测量值在90%特异性时的估计AUC和灵敏度都更高。将得出的TSP切点应用于149名临床诊断为AD的患者（无论其神经病理学诊断如何），3个新皮质区域中TSPs的灵敏度为97%，特异性为84%。因此，基于新皮质区域弥漫性和神经炎型SP的切点能够以高灵敏度和特异性区分非痴呆和AD受试者。
