Cerebral amyloid deposition and diffuse plaques in ''normal'' aging: Evidence for presymptomatic and very mild Alzheimer's disease
Cerebral amyloid deposition and diffuse plaques in ''normal'' aging: Evidence for presymptomatic and very mild Alzheimer's disease
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DOI：
10.1212/wnl.46.3.707
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发表时间：
1996-03-01
期刊：
影响因子：
9.9
通讯作者：
Berg, L
中科院分区：
文献类型：
--
作者：
Morris, JC;Storandt, M;Berg, L
老年斑出现在明显非痴呆的老年人的新皮层中，通常被认为是“正常”衰老的一部分。或者，因为β-淀粉样蛋白的脑沉积可能是阿尔茨海默病（AD）发展的关键机制，所以含有β-淀粉样蛋白的斑块的存在可能代表非常早期的AD。为了研究认知正常老化、阿尔茨海默型极轻度痴呆和新皮质老年斑的存在之间的关系，我们对21名健康老年受试者（死亡时年龄为84.5 ± 6.6岁）进行了纵向研究，并进行了临床病理相关性分析。9名受试者在新皮层中有惊人的高斑块密度;其中2名受试者死于头部损伤，在此之前没有认知障碍的证据。其他7名斑块密度高的受试者在其病程中的某个时间具有非常轻度认知障碍（临床痴呆评定评分为0.5）的临床证据，并且在死亡前的最后一次评估时具有轻度心理测量表现受损。其余12名受试者没有临床或心理障碍，几乎没有或没有新皮质AD病变。这些结果表明，老年斑可能不是正常衰老的一部分，而是表现为症状前或未被识别的早期症状性AD。受试者皮质中高密度的老年斑（主要是弥漫性亚型）正好处于可检测的痴呆阈值，这与β-淀粉样蛋白沉积是AD发展中的初始致病事件的假设一致。
The presence of senile plaques in the neocortex of apparently nondemented elderly persons often is accepted as part of ''normal'' aging. Alternatively, because cerebral deposition of beta-amyloid may be a key mechanism in the development of Alzheimer's disease (AD), the presence of beta-amyloid-containing plaques may represent very early AD. To examine the relationships of cognitively normal aging, very mild dementia of the Alzheimer type, and the presence of neocortical senile plaques, we performed clinicopathologic correlations in 21 longitudinally studied healthy elderly subjects (84.5 +/- 6.6 years old at death). Nine subjects had strikingly high plaque densities in the neocortex; two of these subjects died of head injury before which there was no evidence of cognitive impairment. The other seven subjects with high plaque densities had clinical evidence for very mild cognitive impairment (Clinical Dementia Rating score of 0.5) at some time during their course and mildly impaired psychometric performance at last assessment before death. The remaining 12 subjects had no clinical or psychometric impairment and had few or no neocortical AD lesions. These results suggest that senile plaques may not be part of normal aging but instead represent presymptomatic or unrecognized early symptomatic AD. The high density of senile plaques (predominately of the diffuse subtype) in the cortex of subjects just at the threshold of detectable dementia is consistent with the hypothesis that beta-amyloid deposition is an initial pathogenetic event in the development of AD.