Combined assessment of serum folate and hemoglobin as biomarkers of brain amyloid β accumulation.

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

Patient profiles.

<p>Patient profiles.</p

Prevalence of the APOE-epsilon 4 allele in amyloid positive and amyloid negative patients.

<p>Eight of the 11 (72.7%) amyloid positive patients also carried the APOE-epsilon 4 allele, with it occurring in only one of the six (16.7%) amyloid negative patients. The difference between the two groups was statistically significant (p = 0.027).</p

ROC curve of hemoglobin content.

<p>A ROC curve was constructed to evaluate the diagnostic performance of hemoglobin content in differentiating between amyloid positive patients and amyloid negative patients. The AUC for hemoglobin content was 0.848 [95% CI: 0.661–1.000] (p = 0.021).</p

ROC curve of serum folate levels.

<p>An ROC curve was constructed to evaluate the diagnostic performance of serum folate levels in differentiating between amyloid positive patients and amyloid negative patients. The area under the ROC curve (AUC) for serum folate was 0.136 [95% CI: 0.000–0.312] (p = 0.016).</p

Amyloid PET results of groups defined according to folate state and anaemia state.

<p>Amyloid PET results of groups defined according to folate state and anaemia state.</p

Diagnosis of Pancreatic Neoplasms Using a Novel Method of DNA Methylation Analysis of Mucin Expression in Pancreatic Juice

<div><p>Mucins (MUC) play crucial roles in carcinogenesis and tumor invasion in pancreatic ductal adenocarcinoma (PDAC) and intraductal papillary mucinous neoplasms (IPMNs). Our immunohistochemistry (IHC) studies have shown a consensus position on mucin expression profiles in pancreatic neoplasms as follows: MUC1-positive but MUC2-negative expression in PDACs; MUC1-negative but MUC2-positive expression in intestinal-type IPMNs (dangerous type); MUC1-negative and MUC2-negative expression in gastric-type IPMNs (safe type); High MUC4 expression in PDAC patients with a poor outcome; and MUC4-positive expression in intestinal-type IPMNs. We also showed that three mucin genes (<i>MUC1</i>, <i>MUC2</i> and <i>MUC4</i>) expression in cancer cell line was regulated by DNA methylation. We have developed a novel ‘methylation-specific electrophoresis (MSE)’ method to analyze the DNA methylation status of mucin genes by high sensitivity and resolution. By using the MSE method, we evaluated pancreatic juice samples from 45 patients with various pancreatic lesions. The results were compared with final diagnosis of the pancreatic lesions including IHC of mucin expression in the paired pancreatic tissues. The results indicated that the DNA methylation status of <i>MUC1</i>, <i>MUC2</i> and <i>MUC4</i> in pancreatic juice matched with the mucin expression in tissue. Analyses of the DNA methylation status of <i>MUC1</i>, <i>MUC2</i> and <i>MUC4</i> were useful for differential diagnosis of human pancreatic neoplasms, with specificity and sensitivity of 87% and 80% for PDAC; 100% and 88% for intestinal-type IPMN; and 88% and 77% for gastric-type IPMN, respectively. In conclusion, MSE analysis of human pancreatic juice may provide useful information for selection of treatment for pancreatic neoplasms.</p></div