OBJECTIVES The mechanisms leading to neurodegeneration in Alzheimer's disease (AD) may involve oxidative stress and neuroinflammation. Ceruloplasmin (Cp) is a circulating protein that intersects both these pathways, since its expression is increased during the acute phase response, and the protein acts to lower pro-oxidant iron in cells. Since the role of Cp in AD, and its potential for use as a biomarker is not established, we investigated CSF Cp and its association with longitudinal outcome measures related to AD. METHODS This was an observational study of 268 people from the Alzheimer's Disease Neuroimaging (ADNI) cohort. Subjects were classified clinically as having AD, mild cognitive impairment (MCI) or were cognitively normal (CN), and were also classified as being positive for β-amyloid using established thresholds in the CSF t-tau/Aβ42 ratio. Subjects underwent cognitive tests and MRI studies every 6 months for 2 years, then yearly thereafter for up to 6 years. RESULTS At baseline, CSF Cp was not associated with clinical or pathological diagnosis, but we found an unexpected association between CSF Cp and levels of CSF apolipoprotein E. In longitudinal analysis, high level of CSF Cp was associated with accelerated cognitive decline (as assessed by ADAS-Cog, CDR-SB, and MMSE) and ventricular volume enlargement in people classified as MCI and who had underlying β-amyloid pathology. CONCLUSION These results raise new questions into the role of Cp in neuroinflammation, oxidative stress, and APOE pathways involved in AD, and reveal the potential for this protein to be used as a biomarker in disease prognostication.

中文翻译：

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脑脊液铜蓝蛋白水平可预测患有潜在 β-淀粉样蛋白病理的人的认知能力下降和脑萎缩。

目的 导致阿尔茨海默病 (AD) 神经退行性变的机制可能涉及氧化应激和神经炎症。铜蓝蛋白 (Cp) 是一种循环蛋白，与这两条途径交叉，因为其表达在急性期反应期间增加，并且该蛋白可降低细胞中的促氧化铁。由于 Cp 在 AD 中的作用及其作为生物标志物的潜力尚未确定，我们研究了 CSF Cp 及其与 AD 相关纵向结果测量的关联。方法 这是一项对来自阿尔茨海默病神经影像 (ADNI) 队列的 268 名患者进行的观察性研究。受试者在临床上被分类为患有 AD、轻度认知障碍 (MCI) 或认知正常 (CN)，并且还使用脑脊液 t-tau/Aβ42 比率的既定阈值将受试者分类为 β-淀粉样蛋白阳性。受试者每 6 个月接受一次认知测试和 MRI 研究，持续 2 年，此后每年进行一次，持续长达 6 年。结果 在基线时，CSF Cp 与临床或病理诊断无关，但我们发现 CSF Cp 与 CSF 载脂蛋白 E 水平之间存在意想不到的关联。在纵向分析中，高水平的 CSF Cp 与加速认知衰退相关（通过评估） ADAS-Cog、CDR-SB 和 MMSE）和被归类为 MCI 且患有潜在 β-淀粉样蛋白病理的人群的心室体积增大。结论 这些结果对 Cp 在 AD 相关的神经炎症、氧化应激和 APOE 通路中的作用提出了新的问题，并揭示了该蛋白作为疾病预测生物标志物的潜力。