Stereologic evidence for persistence of viable neurons in layer II of the entorhinal cortex and the CA1 field in Alzheimer disease
Stereologic evidence for persistence of viable neurons in layer II of the entorhinal cortex and the CA1 field in Alzheimer disease
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DOI：
10.1093/jnen/62.1.55
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发表时间：
2003-01-01
影响因子：
3.2
通讯作者：
Morrison, JH
中科院分区：
文献类型：
--
作者：
Hof, PR;Bussière, T;Morrison, JH
内嗅皮层和海马区是最先受到导致阿尔茨海默病(AD)的退行性细胞过程影响的皮质区域，在正常衰老过程中表现出有限程度的神经元变化。一些定量研究报告说，这些区域的神经元大量丧失，神经原纤维缠结(NFT)的数量也相应增加。然而，缺乏关于NFT形成动力学的准确定量数据。在这里，我们对老年对照组和不同程度认知功能障碍的患者进行了细胞内和细胞外(分别为iNFTs和eNFTs)以及内嗅皮层II层和海马CA1区锥体细胞层未受影响神经元的比例的体视学评估。数据显示两个区域的iNFTs和eNFTs的形成率不同，并证实存在严重的与疾病相关的神经元丢失，但与年龄无关。他们还揭示，大量神经元可能不受影响地存在，或者处于NFT形成的过渡阶段，直到AD进展的晚期。在临床痴呆评分为3分的病例中，这些具有生存潜力的神经元占内嗅皮层II层的73%和CA1区的77%。虽然本研究无法评估这些生理学改变的神经元的功能，但这些过渡性神经元可能为旨在保护易受神经纤维变性影响的神经元的潜在治疗干预开辟了新的选择。
The entorhinal cortex and hippocampus are the first cortical regions to be affected by the degenerative cellular process that leads to Alzheimer disease (AD) and display a limited degree of neuronal alterations in normal aging. Several quantitative studies have reported a substantial loss of neurons in these regions and a parallel increase in the number of neurofibrillary tangles (NFTs). However, accurate quantitative data on the dynamics of NFT formation are lacking. Here, we performed a stereologic assessment of the proportions of intracellular and extracellular (ghost) NFTs (iNFTs and eNFTs, respectively) and unaffected neurons in layer II of the entorhinal cortex and in the pyramidal cell layer of the CA1 field of the hippocampus in elderly control cases compared to cases with varying degrees of cognitive dysfunction. The data revealed differential rates of formation of iNFTs and eNFTs between the 2 regions and confirmed the presence of a severe disease-associated, but not age-related, neuronal loss. They also revealed that large numbers of neurons may persist either unaffected or in a transitional stage of NFT formation until the late stages of AD progression. These neurons with viability potential constitute 73% of the total numbers of profiles in layer II of the entorhinal cortex and 77% in the CA1 field in cases with a Clinical Dementia Rating score of 3. Whereas it is not possible in the present study to assess how functional such neurons with altered physiology might be, it is nonetheless likely that these transitional neurons open new options for potential therapeutic interventions aimed at protecting neurons vulnerable to neurofibrillary degeneration.