Kordower J H, Chu Y, Stebbins G T, DeKosky S T, Cochran E J, Bennett D, Mufson E J
Research Center for Brain Repair, Department of Neurological Sciences, Chicago, IL, USA.
Ann Neurol. 2001 Feb;49(2):202-13.
Layer II of the entorhinal cortex contains the cells of origin for the perforant path, plays a critical role in memory processing, and consistently degenerates in end-stage Alzheimer's disease. The extent to which neuron loss in layer II of entorhinal cortex is related to mild cognitive impairment without dementia has not been extensively investigated. We analyzed 29 participants who came to autopsy from our ongoing longitudinal study of aging and dementia composed of religious clergy (Religious Orders Study). All individuals underwent detailed clinical evaluation within 12 months of death and were categorized as having no cognitive impairment (n = 8), mild cognitive impairment (n = 10), or mild or moderate Alzheimer's disease (n = 11). Sections through the entorhinal cortex were immunoreacted with an antibody directed against a neuron-specific nuclear protein (NeuN). Stereological counts of NeuN-immunoreactive stellate cells, their volume, and the volume of layer II entorhinal cortex were estimated. Cases exhibiting no cognitive impairment averaged 639,625 +/- 184,600 layer II stellate neurons in the right entorhinal cortex. Individuals with mild cognitive impairment (63.5%; p < 0.0003) and mild or moderate Alzheimer's disease (46.06%; p < 0.0017) displayed significant losses of layer II entorhinal cortex neurons relative to those with no cognitive impairment but not relative to each other (p > 0.33). There was also significant atrophy of layer II entorhinal cortex neurons in individuals with mild cognitive impairment (24.1%) and Alzheimer's disease (25.1%). The volume of layer II was also reduced in individuals with mild cognitive impairment (26.5%), with a further reduction in those with Alzheimer's disease (46.4%). The loss and atrophy of layer II entorhinal cortex neurons significantly correlated with performance on clinical tests of declarative memory. Atrophy of layer II entorhinal cortex and the neurons within this layer significantly correlated with performance on the Mini Mental Status Examination. These data indicate that atrophy and loss of layer II entorhinal cortex neurons occur in elderly subjects with mild cognitive impairment prior to the onset of dementia and suggests that these changes are not exacerbated in early Alzheimer's disease.
内嗅皮质的第二层包含穿通通路的起源细胞，在记忆处理中起关键作用，并且在晚期阿尔茨海默病中持续退化。内嗅皮质第二层神经元丢失与无痴呆的轻度认知障碍之间的关联程度尚未得到广泛研究。我们分析了来自我们正在进行的由宗教神职人员组成的衰老与痴呆纵向研究（宗教团体研究）中接受尸检的29名参与者。所有个体在死亡后12个月内接受了详细的临床评估，并被分类为无认知障碍（n = 8）、轻度认知障碍（n = 10）或轻度或中度阿尔茨海默病（n = 11）。通过内嗅皮质的切片用针对神经元特异性核蛋白（NeuN）的抗体进行免疫反应。对NeuN免疫反应性星状细胞进行体视学计数，估计它们的体积以及内嗅皮质第二层的体积。无认知障碍的病例右侧内嗅皮质第二层星状神经元平均为639,625±184,600个。轻度认知障碍个体（63.5%；p < 0.0003）和轻度或中度阿尔茨海默病个体（46.06%；p < 0.0017）相对于无认知障碍个体，内嗅皮质第二层神经元有显著丢失，但两者之间无显著差异（p > 0.33）。轻度认知障碍个体（24.1%）和阿尔茨海默病个体（25.1%）的内嗅皮质第二层神经元也有显著萎缩。轻度认知障碍个体第二层的体积也减少（26.5%），阿尔茨海默病个体中进一步减少（46.4%）。内嗅皮质第二层神经元的丢失和萎缩与陈述性记忆临床测试的表现显著相关。内嗅皮质第二层的萎缩以及该层内的神经元与简易精神状态检查的表现显著相关。这些数据表明，在痴呆发作之前，轻度认知障碍的老年受试者中就出现了内嗅皮质第二层神经元的萎缩和丢失，并且表明这些变化在早期阿尔茨海默病中并未加剧。
