Subicular dendritic arborization in Alzheimer's disease correlates with neurofibrillary tangle density
Subicular dendritic arborization in Alzheimer's disease correlates with neurofibrillary tangle density
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DOI：
10.1016/s0002-9440(10)63518-3
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发表时间：
2003-10-01
影响因子：
6
通讯作者：
Arnold, SE
中科院分区：
文献类型：
--
作者：
Falke, E;Nissanov, J;Arnold, SE
阿尔茨海默病（AD）中PHFtau的细胞内积聚破坏了神经元细胞骨架和其他神经元机制，并导致轴突和树突变性以及神经元死亡。此外，淀粉样蛋白- β (Abeta)已被报道对神经元和神经突有毒。虽然突触前元件的丧失是阿尔茨海默病的一个既定特征，但树突变性的性质和程度却很少被研究。我们使用一种新的高通量定量方法研究了map2免疫反应树突，并测量了AD患者和老年对照者的皮层厚度和neun免疫反应神经元的密度、PHFtau神经原纤维缠结（nft）和枕骨下的a13斑块负担。经萎缩校正后，“树突树突指数”在所有三层的耻骨下均显著降低了66%。层流厚度平均减少33%，神经元密度显著减少约50%。正如预期的那样，nft和β斑块在AD中显著增加。树突乔木指数与NFT密度呈负相关，而与β斑块密度无显著相关性。枕骨下树突丢失的模式以及与NFT密度的相关性分别表明，神经传递失行和内在神经原纤维变性都可能导致AD患者的树突丢失。
intracellular accumulation of PHFtau in Alzheimer's disease (AD) disrupts the neuronal cytoskeleton and other neuronal machinery and contributes to axonal and dendritic degeneration, and neuronal death. Furthermore, amyloid-beta (Abeta) has been reported to be toxic to neurons and neurites. While loss of presynaptic elements is an established feature of AD, the nature and extent of dendritic degeneration has been infrequently studied. We investigated MAP2-immunoreactive dendrites using a novel method of high-throughput quantification and also measured cortical thickness and the densities of NeuN-immunoreactive neurons, PHFtau neurofibrillary tangles (NFTs), and A,13 plaque burden in the subiculum in AD and elderly controls. Corrected for atrophy, the "dendritic arborization index" was significantly reduced by up to 66% in all three layers of the subiculum. Laminar thickness was reduced by an average 33% and there was a marked reduction in neuron density of approximately 50%. As expected, NFTs and Abeta plaques were significantly increased in AD. Dendritic arborization indices negatively correlated with NFT densities while no significant correlations were found with Abeta plaque densities. The pattern of dendritic loss in the subiculum and the correlations with NFT densities respectively suggest that deafferentation and intrinsic neurofibrillary degeneration both may contribute to dendritic loss in AD.