Schneider Thomas Rudolf, Stöckli Luisa, Felbecker Ansgar, Nirmalraj Peter Niraj
Department of Neurology, Cantonal Hospital St. Gallen, St. Gallen CH-9007, Switzerland.
Transport at Nanoscale Interfaces Laboratory, Swiss Federal Laboratories for Materials Science and Technology, Dübendorf CH-8600, Switzerland.
Brain Commun. 2024 Jun 13;6(3):fcae180. doi: 10.1093/braincomms/fcae180. eCollection 2024.
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.
像阿尔茨海默病这样的神经退行性疾病的特征是大脑中错误折叠的蛋白质聚集成纤维状。原子力显微镜是一种纳米级成像技术，可用于分辨和量化从寡聚体到纤维状的蛋白质聚集体。最近，我们用原子力显微镜对神经认知障碍患者红细胞表面吸附的蛋白质纤维状聚集体进行了表征，提示了一种新型的阿尔茨海默病生物标志物。然而，健康成年人中红细胞上纤维状沉积物与年龄的关联尚未得到详细研究。在此，我们用原子力显微镜观察并量化了50名健康成年人和37名记忆门诊患者红细胞上的纤维覆盖情况。纤维状蛋白质沉积物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，尤其是那些脑脊液淀粉样β蛋白1-42/1-40比值呈阳性所证实的阿尔茨海默病患者。在健康个体或阿尔茨海默病患者中，红细胞表面纤维的患病率与年龄均无显著相关性。阿尔茨海默病患者与淀粉样蛋白阴性患者红细胞上纤维患病率的重叠表明，红细胞上的纤维沉积可能发生在各种神经退行性疾病中。量化红细胞蛋白质纤维形态和红细胞上的患病率可作为神经退行性变的敏感生物标志物，区分健康个体和神经退行性疾病患者。未来在大规模研究中将原子力显微镜与免疫荧光技术相结合的研究可能会进一步确定这些纤维的化学性质，为神经退行性疾病建立一个全面的、非侵入性的生物标志物平台铺平道路。
