Mikkonen M, Alafuzoff I, Tapiola T, Soininen H, Miettinen R
Department of Neuroscience and Neurology, Kuopio University Hospital and University of Kuopio, Finland.
Neuroscience. 1999;92(2):515-32. doi: 10.1016/s0306-4522(99)00047-0.
The entorhinal cortex, which is involved in neural systems related to memory, is selectively degenerated in early Alzheimer's disease. Here, we examined neuropathological changes in the eight entorhinal subfields in post mortem Alzheimer's disease subjects using Thionin and Bielschowsky stains and parvalbumin, calretinin and calbindin-D28k immunohistochemistry. Both histological stains revealed the most dramatic cell loss and neurofibrillary tangle formation to be in layers II and V of the lateral, intermediate and caudal subfields. In accordance, immunohistochemical staining showed that neurons and fibres that contain calcium-binding proteins were also more frequently altered in these subfields than in the rostromedial subfields. Detailed analysis further revealed that non-principal cells containing parvalbumin or calbindin-D28k showed morphological alterations early in the entorhinal pathology of Alzheimer's disease, whereas non-principal neurons containing calretinin were better preserved even in Alzheimer's disease patients with severe entorhinal pathology. The degeneration of parvalbumin-immunoreactive neurons and basket-like networks and calbindin-positive non-principal neurons was observed mainly in layer II, where the calretinin-positive non-principal neurons formed aggregates especially at late stages of the disease. The pyramidal-shaped neurons containing either calretinin or calbindin-D28k were often preserved, although morphological alterations were observed. Our findings indicate that specific subfields of the entorhinal cortex involving neurons that contain distinct calcium-binding proteins are differentially vulnerable in Alzheimer's disease. This could have an impact on the topographically organized inputs and outputs of the entorhinal cortex in Alzheimer's patients.
内嗅皮质参与与记忆相关的神经系统，在早期阿尔茨海默病中会选择性退化。在此，我们使用硫堇和 Bielschowsky 染色以及小白蛋白、钙视网膜蛋白和钙结合蛋白-D28k 免疫组织化学方法，研究了阿尔茨海默病患者死后内嗅皮质八个亚区的神经病理学变化。两种组织学染色均显示，外侧、中间和尾侧亚区的 II 层和 V 层细胞丢失最为显著，神经原纤维缠结形成也最多。相应地，免疫组织化学染色显示，与吻内侧亚区相比，这些亚区中含有钙结合蛋白的神经元和纤维也更频繁地发生改变。详细分析进一步表明，含有小白蛋白或钙结合蛋白-D28k 的非主细胞在阿尔茨海默病的内嗅病理早期就出现形态改变，而含有钙视网膜蛋白的非主神经元即使在患有严重内嗅病理的阿尔茨海默病患者中也保存得较好。小白蛋白免疫反应性神经元和篮状网络以及钙结合蛋白阳性非主神经元的退化主要在 II 层观察到，而钙视网膜蛋白阳性非主神经元尤其在疾病晚期形成聚集。含有钙视网膜蛋白或钙结合蛋白-D28k 的锥体细胞通常得以保留，尽管观察到了形态改变。我们的研究结果表明，内嗅皮质中涉及含有不同钙结合蛋白的神经元的特定亚区在阿尔茨海默病中易损性不同。这可能会对阿尔茨海默病患者内嗅皮质的拓扑组织输入和输出产生影响。
