Subregional Density of Neurons, Neurofibrillary Tangles and Amyloid Plaques in the Hippocampus of Patients With Alzheimer's Disease
Subregional Density of Neurons, Neurofibrillary Tangles and Amyloid Plaques in the Hippocampus of Patients With Alzheimer's Disease
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DOI：
10.3389/fnana.2019.00099
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发表时间：
2019-12-19
影响因子：
2.9
通讯作者：
Alonso-Nanclares, Lidia
中科院分区：
文献类型：
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作者：
Furcila, Diana;Dominguez-Alvaro, Marta;Alonso-Nanclares, Lidia
在阿尔茨海默病（AD）患者的海马结构中已经报道了各种解剖学改变，并且这些改变与疾病早期的认知症状相关。AD的主要标志是神经元内存在成对的tau蛋白螺旋丝（PHFTau），也称为神经元缠结（NFT），以及在细胞外间隙中形成斑块的淀粉样β蛋白（A β）聚集体。然而，斑块和NFT的密度如何与细胞损失和认知能力下降的严重程度相关尚不清楚。本研究的目的是进一步研究A β斑块和NFT与11例痴呆AD患者的几个海马区（DG，CA 3，CA 1和下托）神经元丢失的可能关系。为此目的，使用体视学技术，我们比较了神经元密度（Nissl染色的和NeuN的免疫反应性神经元）与：（i）针对PHFTau的两种同种型（PHFTau-AT 8和PHFTau-pS396）免疫染色的神经元的数量;和（ii）A β斑块的数量。我们发现，CA 1显示最高数量的NFT和A β斑块，而DG和CA 3显示最低数量的这些标记物。此外，AD患者表现出可变的神经元损失在CA 1由于缠结相关的细胞死亡，这似乎与细胞外缠结的存在。
A variety of anatomical alterations have been reported in the hippocampal formation of patients with Alzheimer's Disease (AD) and these alterations have been correlated with cognitive symptoms in the early stages of the disease. Major hallmarks in AD are the presence of paired helical filaments of tau protein (PHFTau) within neurons, also known as neurofibrillary tangles (NFTs), and aggregates of amyloid-beta protein (A beta) which form plaques in the extracellular space. Nevertheless, how the density of plaques and NFTs relate to the severity of cell loss and cognitive decline is not yet clear. The aim of the present study was to further examine the possible relationship of both A beta plaques and NFTs with neuronal loss in several hippocampal fields (DG, CA3, CA1, and subiculum) of 11 demented AD patients. For this purpose, using stereological techniques, we compared neuronal densities (Nissl-stained, and immunoreactive neurons for NeuN) with: (i) numbers of neurons immunostained for two isoforms of PHFTau (PHFTau-AT8 and PHFTau-pS396); and (ii) number of A beta plaques. We found that CA1 showed the highest number of NFTs and A beta plaques, whereas DG and CA3 displayed the lowest number of these markers. Furthermore, AD patients showed a variable neuronal loss in CA1 due to tangle-related cell death, which seems to correlate with the presence of extracellular tangles.