Aβ43 is more frequent than Aβ40 in amyloid plaque cores from Alzheimer disease brains
Aβ43 is more frequent than Aβ40 in amyloid plaque cores from Alzheimer disease brains
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DOI：
10.1111/j.1471-4159.2009.06170.x
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发表时间：
2009-07-01
影响因子：
4.7
通讯作者：
Tjernberg, Lars O.
中科院分区：
文献类型：
--
作者：
Welander, Hedvig;Franberg, Jenny;Tjernberg, Lars O.
阿尔茨海默病(AD)的一个特征是老年斑中淀粉样β蛋白(Aβ)的细胞外沉积。产生两种主要形式的Aβ，40(Aβ40)和42(Aβ42)残基长。Aβ最丰富的形式是Aβ40，而Aβ42更疏水，更容易形成有毒低聚物，以及在早期斑块形成中特别重要的物种。因此，疏水C末端的长度似乎对Aβ肽的齐聚和神经毒性非常重要。在这里，我们调查了哪些Aβ物质沉积在AD脑中。我们分析了从散发性和家族性AD患者的枕叶和额叶皮质制备的斑块核心，并使用Aβ标准多肽进行了定量研究。用溴化氰产生C-末端Aβ片段，用高效液相色谱与电喷雾离子陷阱质谱仪联用进行分析。我们发现一种更长的多肽，Aβ43，比Aβ40更频繁。在任何一个大脑中都没有观察到比Aβ43更长的变异。进行了免疫组织化学检查，结果与我们的发现一致。Aβ1-43迅速聚合，我们认为这种变异可能在AD中起重要作用。
One hallmark of Alzheimer disease (AD) is the extracellular deposition of the amyloid beta-peptide (A beta) in senile plaques. Two major forms of A beta are produced, 40 (A beta 40) and 42 (A beta 42) residues long. The most abundant form of A beta is A beta 40, while A beta 42 is more hydrophobic and more prone to form toxic oligomers and the species of particular importance in early plaque formation. Thus, the length of the hydrophobic C-terminal seems to be very important for the oligomerization and neurotoxicity of the A beta peptide. Here we investigated which A beta species are deposited in AD brain. We analyzed plaque cores, prepared from occipital and frontal cortex, from sporadic and familial AD cases and performed a quantitative study using A beta standard peptides. Cyanogen bromide was used to generate C-terminal A beta fragments, which were analyzed by HPLC coupled to an electrospray ionisation ion trap mass spectrometer. We found a longer peptide, A beta 43, to be more frequent than A beta 40. No variants longer than A beta 43 could be observed in any of the brains. Immunohistochemistry was performed and was found to be in line with our findings. A beta 1-43 polymerizes rapidly and we suggest that this variant may be of importance for AD.