Yoshinaga Takuma, Nishimata Hiroto, Kajiya Yoriko, Yokoyama Shunichi
Division of Clinical Application, Nanpuh Hospital, Kagoshima, Japan.
Gastroenterology, Nanpuh Hospital, Kagoshima, Japan.
PLoS One. 2017 Apr 13;12(4):e0175854. doi: 10.1371/journal.pone.0175854. eCollection 2017.
A relationship between Alzheimer's disease (AD) and folate has been reported. Amyloid positron emission tomography (PET) is currently one of the most reliable biomarkers for AD. We investigated the correlation between serum folate levels and amyloid imaging to clarify whether serum folate could be a biomarker for AD. We also examined the usefulness of a combined assessment of serum folate levels and red blood cell hemoglobin content. Apolipoprotein E (APOE) gene polymorphisms were also assessed. Serum folate levels and hemoglobin content were evaluated by receiver operating characteristic analysis for their diagnostic capability as AD biomarkers relating to brain amyloid β accumulation. The area under the ROC curve (AUC) for serum folate was 0.136 (95% confidence interval [CI]: 0.000-0.312; p = 0.016). The AUC for hemoglobin content was 0.848 (95% CI: 0.661-1.000; p = 0.021). Therefore, the folate deficiency with low folate levels or the non-anaemia with high hemoglobin content levels were found to have a high probability of also testing positive for amyloid. Furthermore, eight patients were found to be folate deficiency and non-anaemia, those who were consist of 7 amyloid positive patients (87.5%), and only one of the amyloid negative patients (12.5%). These results suggest that a deficiency of serum folate and high hemoglobin levels may reflect an increased risk of amyloid β accumulation in the brain. Additionally, we demonstrated that these biomarkers could enhance the effectiveness of APOE as an AD biomarker. This study reveals that the combined assessment of serum folate levels and red blood cell hemoglobin content may be a useful biomarker for amyloid β accumulation in the brain. We also found that the combination of serum folate levels and hemoglobin content is a more specific and sensitive blood biomarker for AD than APOE or folate alone. These findings may be used to support clinical diagnosis of AD using a simple blood test.
已有报道称阿尔茨海默病（AD）与叶酸之间存在关联。淀粉样蛋白正电子发射断层扫描（PET）是目前AD最可靠的生物标志物之一。我们研究了血清叶酸水平与淀粉样蛋白成像之间的相关性，以阐明血清叶酸是否可作为AD的生物标志物。我们还检验了血清叶酸水平与红细胞血红蛋白含量联合评估的效用。同时也评估了载脂蛋白E（APOE）基因多态性。通过接受者操作特征分析评估血清叶酸水平和血红蛋白含量作为与脑淀粉样β蛋白积累相关的AD生物标志物的诊断能力。血清叶酸的ROC曲线下面积（AUC）为0.136（95%置信区间[CI]：0.000 - 0.312；p = 0.016）。血红蛋白含量的AUC为0.848（95%CI：0.661 - 1.000；p = 0.021）。因此，发现叶酸水平低的叶酸缺乏或血红蛋白含量高的非贫血状态很可能淀粉样蛋白检测也呈阳性。此外，发现8例患者为叶酸缺乏且非贫血，其中7例淀粉样蛋白阳性患者（87.5%），只有1例淀粉样蛋白阴性患者（12.5%）。这些结果表明血清叶酸缺乏和高血红蛋白水平可能反映了脑内淀粉样β蛋白积累风险增加。此外，我们证明这些生物标志物可增强APOE作为AD生物标志物的有效性。本研究表明，血清叶酸水平与红细胞血红蛋白含量的联合评估可能是脑内淀粉样β蛋白积累的有用生物标志物。我们还发现，血清叶酸水平与血红蛋白含量的组合作为AD的血液生物标志物比单独的APOE或叶酸更具特异性和敏感性。这些发现可用于支持通过简单的血液检测对AD进行临床诊断。
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