Rak Margaret, Del Bigio Marc R, Mai Sabine, Westaway David, Gough Kathleen
Department of Chemistry, University of Manitoba, Winnipeg, MB, Canada R3T 2N2.
Biopolymers. 2007 Nov;87(4):207-17. doi: 10.1002/bip.20820.
Plaques composed of the Abeta peptide are the main pathological feature of Alzheimer's disease. Dense-core plaques are fibrillar deposits of Abeta, showing all the classical properties of amyloid including beta-sheet secondary structure, while diffuse plaques are amorphous deposits. We studied both plaque types, using synchrotron infrared (IR) microspectroscopy, a technique that allows the chemical composition and average protein secondary structure to be investigated in situ. We examined plaques in hippocampal, cortical and caudal tissue from 5- to 21-month-old TgCRND8 mice, a transgenic model expressing doubly mutant amyloid precursor protein, and displaying impaired hippocampal function and robust pathology from an early age. Spectral analysis confirmed that the congophilic plaque cores were composed of protein in a beta-sheet conformation. The amide I maximum of plaque cores was at 1623 cm(-1), and unlike for in vitro Abeta fibrils, the high-frequency (1680-1690 cm(-1)) component attributed to antiparallel beta-sheet was not observed. A significant elevation in phospholipids was found around dense-core plaques in TgCRND8 mice ranging in age from 5 to 21 months. In contrast, diffuse plaques were not associated with IR detectable changes in protein secondary structure or relative concentrations of any other tissue components.
由β-淀粉样蛋白（Aβ）肽组成的斑块是阿尔茨海默病的主要病理特征。致密核心斑块是Aβ的纤维状沉积物，具有淀粉样蛋白的所有经典特性，包括β-折叠二级结构，而弥漫性斑块是无定形沉积物。我们使用同步辐射红外（IR）显微光谱技术研究了这两种斑块类型，该技术能够原位研究化学成分和平均蛋白质二级结构。我们检查了5至21月龄TgCRND8小鼠海马、皮质和尾部组织中的斑块，该转基因模型表达双突变淀粉样前体蛋白，从小就表现出海马功能受损和严重的病理学特征。光谱分析证实，嗜刚果红斑块核心由处于β-折叠构象的蛋白质组成。斑块核心的酰胺I最大值位于1623 cm-1处，与体外Aβ纤维不同，未观察到归因于反平行β-折叠的高频（1680 - 1690 cm-1）成分。在5至21月龄的TgCRND8小鼠中，发现致密核心斑块周围的磷脂显著升高。相比之下，弥漫性斑块与蛋白质二级结构或任何其他组织成分的相对浓度的红外可检测变化无关。
