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The search for a unique Raman signature of amyloid-beta plaques in human brain tissue from Alzheimer's disease patients.
Analyst ( IF 4.2 ) Pub Date : 2020-01-07 , DOI: 10.1039/c9an02087j
Benjamin Lochocki 1 , Tjado H J Morrema 2 , Freek Ariese 1 , Jeroen J M Hoozemans 2 , Johannes F de Boer 1
Affiliation  

Definite Alzheimer's disease (AD) diagnosis is commonly done on ex vivo brain tissue using immuno-histochemical staining to visualize amyloid-beta (Aβ) aggregates, also known as Aβ plaques. Raman spectroscopy has shown its potential for non-invasive and label-free determination of bio-molecular compositions, aiding the post-mortem diagnosis of pathological tissue. Here, we investigated whether conventional Raman spectroscopy could be used for the detection of amyloid beta deposits in fixed, ex vivo human brain tissue, taken from the frontal cortex region. We examined the spectra and spectral maps of three severe AD cases and two healthy control cases and compared their spectral outcome among each other as well as to recent results in the literature obtained with various spectroscopic techniques. After hyperspectral Raman mapping, Aβ plaques were visualized using Thioflavin-S staining on the exact same tissue sections. As a result, we show that tiny diffuse or tangled-like morphological structures, visible under microscopic conditions on unstained tissue and often but erroneously assumed to be deposits of Aβ, are instead usually an aggregation of highly auto-fluorescent lipofuscin granulates without any, or limited, plaque or plaque-like association. The occurrence of these auto-fluorescent particles is equally distributed in both AD and healthy control cases. Therefore, they cannot be used as possible criteria for Alzheimer's disease diagnosis. Furthermore, a unique plaque-specific/Aβ spectrum could not be determined even after possible spectral interferences were carefully removed.

中文翻译:

在阿尔茨海默氏病患者的人脑组织中寻找淀粉样蛋白β斑块的独特拉曼特征。

阿尔茨海默病(AD)的确诊通常是在离体脑组织上进行的,方法是使用免疫组织化学染色使Aβ斑块(也称为Aβ斑)可视化。拉曼光谱法显示了其潜在的无创且无标记的生物分子成分测定方法,有助于病理组织的验尸诊断。在这里,我们调查了常规拉曼光谱是否可用于检测从额叶皮层区域提取的固定,离体人脑组织中的淀粉样β沉积物。我们检查了三个严重AD病例和两个健康对照例的光谱和谱图,并将它们的光谱结果相互比较,并与通过各种光谱技术获得的文献中的最新结果进行了比较。经过高光谱拉曼映射,使用硫黄素-S染色在完全相同的组织切片上观察Aβ斑块。结果,我们显示出微小的弥散或缠结的形态结构,在微观条件下在未染色的组织上可见,并且经常但被错误地假定为Aβ沉积物,通常是高度自发荧光的脂褐素颗粒的聚集体,没有任何或没有有限的,斑块或斑块状联想。这些自发荧光颗粒的出现在AD和健康对照者中均等分布。因此,它们不能用作阿尔茨海默氏病诊断的可能标准。此外,即使小心地消除了可能的光谱干扰,也无法确定独特的噬斑特异性/Aβ光谱。我们发现微小的弥散或缠结的形态结构在显微镜下可见于未染色的组织上,通常但被错误地假定为Aβ沉积物,而通常是高度自发荧光的脂褐素颗粒的聚集体,没有任何或有限的噬斑或斑块状联想。这些自发荧光颗粒的出现在AD和健康对照者中均等分布。因此,它们不能用作阿尔茨海默氏病诊断的可能标准。此外,即使小心地消除了可能的光谱干扰,也无法确定独特的噬斑特异性/Aβ光谱。我们发现微小的弥散或缠结的形态结构,在显微镜下未染色的组织上可见,经常但被错误地假定为Aβ沉积物,通常是高度自发荧光的脂褐素颗粒的聚集体,没有任何或有限的噬菌斑或斑块状联想。这些自发荧光颗粒的出现在AD和健康对照者中均等分布。因此,它们不能用作阿尔茨海默氏病诊断的可能标准。此外,即使小心地消除了可能的光谱干扰,也无法确定独特的噬斑特异性/Aβ光谱。相反,它们通常是高度自发荧光的脂褐素颗粒的聚集体,没有任何或有限的噬斑或噬斑样结合。这些自发荧光颗粒的出现在AD和健康对照者中均等分布。因此,它们不能用作阿尔茨海默氏病诊断的可能标准。此外,即使小心地消除了可能的光谱干扰,也无法确定独特的噬斑特异性/Aβ光谱。相反,它们通常是高度自发荧光的脂褐素颗粒的聚集体,没有任何或有限的噬斑或噬斑样结合。这些自发荧光颗粒的出现在AD和健康对照者中均等分布。因此,它们不能用作阿尔茨海默氏病诊断的可能标准。此外,即使小心地消除了可能的光谱干扰,也无法确定独特的噬斑特异性/Aβ光谱。
更新日期:2020-03-03
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