Three-dimensional analysis of synapses in the transentorhinal cortex of Alzheimer's disease patients.
Three-dimensional analysis of synapses in the transentorhinal cortex of Alzheimer's disease patients.
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DOI：
10.1186/s40478-018-0520-6
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发表时间：
2018-03-02
影响因子：
7.1
通讯作者：
Alonso-Nanclares L
中科院分区：
文献类型：
--
作者：
Domínguez-Álvaro M;Montero-Crespo M;Blazquez-Llorca L;Insausti R;DeFelipe J;Alonso-Nanclares L
阿尔茨海默病(AD)早期的突触功能障碍或丢失被认为是认知功能障碍的主要结构相关性。情景记忆的早期丧失与内侧颞叶(MTL)结构的进行性变性密切相关，经鼻中脑皮质(TEC)是MTL结构的首发区。然而，在AD患者的人脑样本中，还没有对这一区域进行超微结构研究。在本研究中，我们使用聚焦离子束/扫描电子显微镜(FIB/SEM)进行了详细的三维(3D)超微结构分析，以研究AD患者TEC中可能的突触变化。令人惊讶的是，对神经束内突触的密度、形态特征和空间分布的分析显示，AD和对照样本之间没有显著差异。但光镜观察显示，AD组TEC皮质厚度明显变薄，但神经元、神经胶质细胞体、血管和神经纤维束的体积无明显变化。因此，目前的结果表明，突触的绝对数量急剧减少，而突触连接的形态和突触的空间分布保持不变。这些变化如何影响阿尔茨海默病患者的认知损害仍有待阐明。本文的在线版本(10.1186/s40478-0180520-6)包含补充材料，可供授权用户使用。
Synaptic dysfunction or loss in early stages of Alzheimer’s disease (AD) is thought to be a major structural correlate of cognitive dysfunction. Early loss of episodic memory, which occurs at the early stage of AD, is closely associated with the progressive degeneration of medial temporal lobe (MTL) structures of which the transentorhinal cortex (TEC) is the first affected area. However, no ultrastructural studies have been performed in this region in human brain samples from AD patients. In the present study, we have performed a detailed three-dimensional (3D) ultrastructural analysis using focused ion beam/scanning electron microscopy (FIB/SEM) to investigate possible synaptic alterations in the TEC of patients with AD. Surprisingly, the analysis of the density, morphological features and spatial distribution of synapses in the neuropil showed no significant differences between AD and control samples. However, light microscopy studies showed that cortical thickness of the TEC was severely reduced in AD samples, but there were no changes in the volume occupied by neuronal and glial cell bodies, blood vessels, and neuropil. Thus, the present results indicate that there is a dramatic loss of absolute number of synapses, while the morphology of synaptic junctions and synaptic spatial distribution are maintained. How these changes affect cognitive impairment in AD remains to be elucidated. The online version of this article (10.1186/s40478-018-0520-6) contains supplementary material, which is available to authorized users.
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影响因子：
4.8
作者：
Ding, Song-Lin;Van Hoesen, Gary W.
通讯作者：
Van Hoesen, Gary W.
DOI：
10.1073/pnas.0803652105
发表时间：
2008-09-23
影响因子：
11.1
作者：
Alonso-Nanclares, L.;Gonzalez-Soriano, J.;DeFelipe, J.
通讯作者：
DeFelipe, J.
DOI：
10.1097/nen.0b013e318232a379
发表时间：
2011-11-01
影响因子：
3.2
作者：
Braak, Heiko;Thal, Dietmar R.;Del Tredici, Kelly
通讯作者：
Del Tredici, Kelly
影响因子：
12.7
作者：
BRAAK, H;BRAAK, E
通讯作者：
BRAAK, E
影响因子：
12.7
作者：
Dorostkar MM;Zou C;Blazquez-Llorca L;Herms J
通讯作者：
Herms J