Amyloid-β E22Δ variant induces synaptic alteration in mouse hippocampal slices
Amyloid-β E22Δ variant induces synaptic alteration in mouse hippocampal slices
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DOI：
10.1097/wnr.0b013e3282fb78c4
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发表时间：
2008-04-16
期刊：
影响因子：
1.7
通讯作者：
Tomiyama, Takami
中科院分区：
文献类型：
--
作者：
Takuma, Hiroshi;Teraoka, Rie;Tomiyama, Takami
我们最近在家族性阿尔茨海默型痴呆中发现了一种新的淀粉样前体蛋白突变(E693 Delta)。这种突变产生缺乏谷氨酸-22(E22 Delta)的淀粉样β蛋白(Aβ)变异体，它表现出增强的寡聚化但没有纤化。在这里，我们检测了AβE22 Delta多肽的体外毒性。在3-(4，5-二甲基噻唑-2基)-2，5-二苯基四氮唑溴化法中，野生型Aβ1-42对培养的神经细胞表现出剂量依赖性(1 NM到1 mU)的细胞毒性，而Aβ1-42 E22 Delta仅在1mM时表现出微弱的毒性。而野生型Aβ1-42在0.1-1微米处是营养的，在10微米处是有毒的。这些结果表明，细胞外AβE22 Delta比野生型Aβ引起更有效的突触改变，但神经变性更少，可能是因为其独特的聚集特性。
We recently identified a novel amyloid precursor protein mutation (E693 Delta) in familial Alzheimer's-type dementia. This mutation produces amyloid-beta (A beta) variant lacking glutamate-22 (E22 Delta), which showed enhanced oligomerization but no fibrillization. Here, we examined in-vitro toxicity of A beta E22 Delta peptide. Wild-type A beta 1-42 showed a dose-dependent (1 nM to 1 mu M) cytotoxicity to cultured neuronal cells in the 3-(4,5-dimethylthiazol-2yl)-2,5-diphenyl tetrazolium bromide assay, whereas A beta 1-42 E22 Delta was toxic only weakly at 1 mu M. In mouse hippocampal slices, however, A beta 1-42 E22 Delta caused a dose-dependent (0.1-10 mu M) decrease of synaptophysin, whereas wild-type A beta 1-42 was trophic at 0.1-1 mu M and toxic at 10 mu M. These results suggest that extracellular A beta E22 Delta causes more potent synaptic alteration, but lower neurodegeneration, than wild-type A beta probably because of its unique aggregation property.