Quantifying physical differences of protein aggregates implicated in Alzheimer’s disease (AD), in blood, could provide crucial information on disease stages. Here, red blood cells (RBCs) from 50 patients with neurocognitive complaints and 16 healthy individuals were profiled using an atomic force microscope (AFM). AFM measurements revealed patient age– and stage of neurocognitive disorder–dependent differences in size, shape, morphology, assembly, and prevalence of protein aggregates on RBCs, referred to as physical biomarkers. Crystals composed of fibrils were exclusively detected on RBCs for AD patients aged above 80 years. Fibril prevalence was negatively correlated with the cerebrospinal fluid (CSF) β-amyloid (Aβ) 42/40 ratio and was observed to be higher in the Aβ-positive patient category. Using a cutoff of ≥40% fibril prevalence, the CSF Aβ status was classified with 88% accuracy (sensitivity 100%, specificity 73%). The merits and challenges in integrating physical biomarkers in AD diagnosis are discussed.

中文翻译：

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红细胞上蛋白质聚集体的空间组织作为阿尔茨海默病病理学的物理生物标志物

量化血液中与阿尔茨海默病 (AD) 相关的蛋白质聚集体的物理差异，可以提供有关疾病阶段的重要信息。在这里，使用原子力显微镜 (AFM) 分析了来自 50 名患有神经认知疾病的患者和 16 名健康个体的红细胞 (RBC)。AFM 测量揭示了患者年龄和神经认知障碍阶段在大小、形状、形态、组装和红细胞上蛋白质聚集体（称为物理生物标志物）的流行方面的差异。仅在 80 岁以上的 AD 患者的红细胞上检测到由原纤维组成的晶体。原纤维患病率与脑脊液 (CSF) β-淀粉样蛋白 (Aβ) 42/40 比率呈负相关，并且在 Aβ 阳性患者类别中观察到更高。使用 ≥ 40% 原纤维流行率的截止值，CSF Aβ 状态的分类准确率为 88%（灵敏度 100%，特异性 73%）。讨论了将物理生物标志物整合到 AD 诊断中的优点和挑战。