University of Exeter, School of Physics and Astronomy, Exeter EX4 4QL, UK.
Analyst. 2018 Feb 12;143(4):850-857. doi: 10.1039/c7an01747b.
Recent work using micro-Fourier transform infrared (μFTIR) imaging has revealed that a lipid-rich layer surrounds many plaques in post-mortem Alzheimer's brain. However, the origin of this lipid layer is not known, nor is its role in the pathogenesis of Alzheimer's disease (AD). Here, we studied the biochemistry of plaques in situ using a model of AD. We combined FTIR, Raman and immunofluorescence images, showing that astrocyte processes co-localise with the lipid ring surrounding many plaques. We used μFTIR imaging to rapidly measure chemical signatures of plaques over large fields of view, and selected plaques for higher resolution analysis with Raman microscopy. Raman maps showed similar lipid rings and dense protein cores as in FTIR images, but also revealed cell bodies. We confirmed the presence of plaques using amylo-glo staining, and detected astrocytes using immunohistochemistry, revealing astrocyte co-localisation with lipid rings. This work is important because it correlates biochemical changes surrounding the plaque with the biological process of astrogliosis.
最近使用微傅里叶变换红外(μFTIR)成像的研究揭示了富含脂质的层围绕着许多阿尔茨海默病大脑中的斑块。然而,这个脂质层的起源尚不清楚,其在阿尔茨海默病(AD)发病机制中的作用也不清楚。在这里,我们使用 AD 模型研究了斑块的生物化学。我们结合 FTIR、拉曼和免疫荧光图像,显示星形胶质细胞过程与许多斑块周围的脂质环共定位。我们使用 μFTIR 成像快速测量大视场斑块的化学特征,并选择拉曼显微镜进行更高分辨率分析的斑块。拉曼图谱显示出与 FTIR 图像相似的脂质环和密集的蛋白质核心,但也显示出细胞体。我们使用淀粉样蛋白染色证实了斑块的存在,并通过免疫组织化学检测到星形胶质细胞,揭示了星形胶质细胞与脂质环的共定位。这项工作很重要,因为它将斑块周围的生化变化与星形胶质细胞增生的生物学过程相关联。