Elevated plasma ferritin in elderly individuals with high neocortical amyloid-β load
Elevated plasma ferritin in elderly individuals with high neocortical amyloid-β load
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DOI：
10.1038/mp.2017.146
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发表时间：
2018-08-01
影响因子：
11
通讯作者：
Martins, R. N.
中科院分区：
文献类型：
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作者：
Goozee, K.;Chatterjee, P.;Martins, R. N.
铁蛋白是一种铁储存和调节蛋白，与阿尔茨海默病（AD）相关;然而，在认知障碍之前，尚未在临床前AD中对其进行研究，通过新皮质淀粉样蛋白-β负荷（NAL）检测。对克尔圣公会退休村老龄健康倡议队列的参与者进行了血浆和血清铁蛋白的横断面分析。受试者年龄为65-90岁，并通过正电子发射断层扫描使用标准摄取值比率截止值= 1.35分为高和低NAL组。与NAL低的受试者相比，NAL高的受试者铁蛋白显著升高，校正了协变量年龄，性别，载脂蛋白E β 4携带和C反应蛋白（炎症标志物）水平。铁蛋白也被观察到与NAL正相关。基于相同协变量的逻辑回归的受试者工作特征曲线（基础模型），区分NAL高低（曲线下面积（AUC）= 0.766），但当将血浆铁蛋白加入基础模型时，（AUC= 0.810），使得在75%的灵敏度下，将铁蛋白添加到基础模型时特异性从62%增加到71%，这表明铁蛋白是超过基础模型的NAL的统计学显著的额外预测因子。然而，与基础模型相比，铁蛋白单独的贡献相对较小。目前的研究结果表明，铁动员受损是AD发病机制的早期事件。本研究的观察结果突出了铁蛋白对临床前AD的血液生物标志物的潜力。
Ferritin, an iron storage and regulation protein, has been associated with Alzheimer's disease (AD); however, it has not been investigated in preclinical AD, detected by neocortical amyloid-beta load (NAL), before cognitive impairment. Cross-sectional analyses were carried out for plasma and serum ferritin in participants in the Kerr Anglican Retirement Village Initiative in Aging Health cohort. Subjects were aged 65-90 years and were categorized into high and low NAL groups via positron emission tomography using a standard uptake value ratio cutoff= 1.35. Ferritin was significantly elevated in participants with high NAL compared with those with low NAL, adjusted for covariates age, sex, apolipoprotein E epsilon 4 carriage and levels of C-reactive protein (an inflammation marker). Ferritin was also observed to correlate positively with NAL. A receiver operating characteristic curve based on a logistic regression of the same covariates, the base model, distinguished high from low NAL (area under the curve (AUC) = 0.766), but was outperformed when plasma ferritin was added to the base model (AUC= 0.810), such that at 75% sensitivity, the specificity increased from 62 to 71% on adding ferritin to the base model, indicating that ferritin is a statistically significant additional predictor of NAL over and above the base model. However, ferritin's contribution alone is relatively minor compared with the base model. The current findings suggest that impaired iron mobilization is an early event in AD pathogenesis. Observations from the present study highlight ferritin's potential to contribute to a blood biomarker panel for preclinical AD.