Neuropathologic criteria for diagnosing Alzheimer disease in persons with pure dementia of Alzheimer type
Neuropathologic criteria for diagnosing Alzheimer disease in persons with pure dementia of Alzheimer type
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DOI：
10.1093/jnen/63.10.1028
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发表时间：
2004-10-01
影响因子：
3.2
通讯作者：
Morris, JC
中科院分区：
文献类型：
--
作者：
McKeel, DW;Price, JL;Morris, JC
目前还没有公认的神经病理学标准来区分阿尔茨海默病（AD）和健康的脑老化。我们使用严格定义的非痴呆（n = 7）和AD（n = 35）受试者（无已知共病），检验了Bielschowsky银染色的总老年斑、核心老年斑和神经炎性老年斑（分别为TSP、CSP和NSP）而不是神经纤维缠结（NFT）最能区分这两种疾病的假设。我们比较了3个新皮质区，海马CA 1区，内嗅皮质病变的19名男性和13名女性之间的74和86岁的死亡。临床痴呆评分（CDR）用于评估死亡一年内的认知障碍程度。新皮质TSP测量与呼气CDR的相关性最高：曲线下面积（AUC）= 0.986，90%特异性时的灵敏度为97.8%，估计临界点为6.0 TSP/ mm（2）。与NFT相比，所有SP测量产生了更高的估计AUC和90%特异性的灵敏度。推导出的TSP临界点应用于149人的临床AD，无论他们的神经病理诊断产生了97%的灵敏度和特异性的TSP在3个新皮质区的84%。因此，基于新皮质区弥漫性和神经炎性SP的临界点区分非痴呆和AD受试者具有较高的敏感性和特异性。
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/ mm(2). 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.