PDF(Pubmed)
Abstract：
Neurodegenerative diseases like Alzheimer\'s disease are characterized by the accumulation of misfolded proteins into fibrils in the brain. Atomic force microscopy is a nanoscale imaging technique that can be used to resolve and quantify protein aggregates from oligomers to fibrils. Recently, we characterized protein fibrillar aggregates adsorbed on the surface of red blood cells with atomic force microscopy from patients with neurocognitive disorders, suggesting a novel Alzheimer\'s disease biomarker. However, the age association of fibril deposits on red blood cells has not yet been studied in detail in healthy adults. Here, we used atomic force microscopy to visualize and quantify fibril coverage on red blood cells in 50 healthy adults and 37 memory clinic patients. Fibrillar protein deposits sporadically appeared in healthy individuals but were much more prevalent in patients with neurodegenerative disease, especially those with Alzheimer\'s disease as confirmed by positive CSF amyloid beta 1-42/1-40 ratios. The prevalence of fibrils on the red blood cell surface did not significantly correlate with age in either healthy individuals or Alzheimer\'s disease patients. The overlap in fibril prevalence on red blood cells between Alzheimer\'s disease and amyloid-negative patients suggests that fibril deposition on red blood cells could occur in various neurodegenerative diseases. Quantifying red blood cell protein fibril morphology and prevalence on red blood cells could serve as a sensitive biomarker for neurodegeneration, distinguishing between healthy individuals and those with neurodegenerative diseases. Future studies that combine atomic force microscopy with immunofluorescence techniques in larger-scale studies could further identify the chemical nature of these fibrils, paving the way for a comprehensive, non-invasive biomarker platform for neurodegenerative diseases.
摘要：
神经退行性疾病如阿尔茨海默病的特征在于错误折叠的蛋白质在大脑中积累到原纤维中。原子力显微镜是一种纳米级成像技术，可用于解析和量化从寡聚体到原纤维的蛋白质聚集体。最近,我们用原子力显微镜表征了神经认知障碍患者红细胞表面吸附的蛋白纤维状聚集体，提示一种新的阿尔茨海默病生物标志物。然而,尚未在健康成年人中详细研究红细胞上原纤维沉积的年龄相关性。这里,我们使用原子力显微镜观察和量化50例健康成人和37例记忆门诊患者红细胞上的原纤维覆盖率.纤维蛋白沉积偶尔出现在健康个体中，但在神经退行性疾病患者中更为普遍。尤其是那些患有阿尔茨海默病的患者，如脑脊液淀粉样蛋白β1-42/1-40比值阳性所证实。在健康个体或阿尔茨海默病患者中，红细胞表面原纤维的患病率与年龄没有显着相关。阿尔茨海默氏病和淀粉样蛋白阴性患者之间的红细胞原纤维患病率重叠表明，在各种神经退行性疾病中都可能发生红细胞原纤维沉积。定量红细胞蛋白原纤维形态和红细胞上的患病率可以作为神经变性的敏感生物标志物。区分健康个体和患有神经退行性疾病的个体。未来将原子力显微镜与免疫荧光技术相结合的大规模研究可以进一步确定这些原纤维的化学性质，为全面、神经退行性疾病的非侵入性生物标志物平台。
