Neurochemical dissection of synaptic pathology in Alzheimer's disease.
Neurochemical dissection of synaptic pathology in Alzheimer's disease.
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DOI：
10.1017/s1041610298005110
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发表时间：
1998-03-01
影响因子：
7
通讯作者：
Blennow, K
中科院分区：
文献类型：
--
作者：
Davidsson, P;Blennow, K
突触病理学作为阿尔茨海默病（AD）发病机制的核心，已得到越来越多的关注。为了解决AD中的突触病理是否涉及整个突触或仅限于其特定组分的问题，我们研究了三种不同的突触囊泡蛋白（rab 3a，突触结合蛋白，突触素）以及突触前膜蛋白GAP-43和突触后蛋白神经颗粒蛋白。材料包括8例早发性AD（EAD）患者、11例晚发性AD（LAD）患者、6例血管性痴呆（VAD）患者和9例对照组的尸检脑组织（额叶皮质、海马和小脑）。在AD中发现了所有突触蛋白的减少，在EAD中比在LAD中更明显，在额叶皮层（EAD 30%至70% vs. LAD 82%至88%的对照值）和海马（EAD 22%至82% vs. LAD 76%至89%的对照值）中，而在VAD中仅发现了微小的变化。所有突触蛋白在AD中减少的发现表明整个突触元件的变性和丢失在EAD中比在LAD中更明显。
Synaptic pathology has attained increasing attention as being central in the pathogenesis of Alzheimer's disease (AD). To address the question whether synaptic pathology in AD involves the whole synapse, or is limited to specific components thereof, we studied three different synaptic vesicle proteins (rab3a, synaptotagmin, synaptophysin) and also the presynaptic membrane protein GAP-43 and the postsynaptic protein neurogranin. The material included postmortem brain tissue (frontal cortex, hippocampus, and cerebellum) from 8 patients with early-onset AD (EAD), 11 patients with late-onset AD (LAD), 6 patients with vascular dementia (VAD), and 9 control subjects. A reduction of all synaptic proteins was found in AD, more pronounced in EAD than in LAD, in both the frontal cortex (EAD 30% to 70% vs. LAD 82% to 88% of control value) and hippocampus (EAD 22% to 82% vs. LAD 76% to 89% of control value), whereas only minor changes were found in VAD. The finding that all synaptic proteins were reduced in AD suggests a degeneration and loss of whole synaptic elements that are more pronounced in EAD than in LAD.