8 research outputs found
Effects of super-hard rice bread blended with black rice bran on amyloid β peptide production and abrupt increase in postprandial blood glucose levels in mice
<p>Alzheimer’s disease and type 2 diabetes are very serious diseases with the latter having been suggested to cause the former. We prepared super-hard rice bread blended with black rice bran (SRBBB), which contained a high amount of resistant starch that showed strong inhibitory activities against β-secretase and acetylcholinesterase even after heating. Black rice bran showed greater β-secretase inhibitory activity (3.6-fold) than Koshihikari rice. The bran contained more oleic acid and anthocyanin, meaning that it is potentially a biofunctional food with a high antioxidant capacity. Furthermore, aged mice, which were fed a SRBBB diet for four weeks, showed lower amyloid <i>β</i> 40 peptide in the blood than mice fed a commercial diet (<i>p</i> < 0.01). Additionally, their initial blood glucose levels (BGLs) after 12 weeks of being fed SRBBB were significantly lower than those in the control group. Taken together, our results indicate SRBBB shows promise for inhibiting not only amyloid <i>β</i> production, but also abrupt increases in postprandial BGLs.</p> <p>Characterization of amyloid β-40 protein species with ELISA method.</p
Additional file 2: Table S1. of Serum microRNA miR-501-3p as a potential biomarker related to the progression of Alzheimer’s disease
Top 20 deregulated serum miRNAs that were identified by NGS in the ROW discovery set after adjusting for age, sex, APOE genotype, and hemolysis ratio. Table S2. Significantly deregulated miRNAs that were identified by NGS in the temporal cortex of the ROW discovery set. Table S3. Significantly deregulated miRNAs that were identified by NGS in the temporal cortex of the ROW discovery set after adjusting for age, sex, APOE genotype, and RIN. Table S4. Significantly differentially expressed genes that were identified by NGS in hsa-miR-501-3p overexpression in cultured cells. Table S5. Gene Ontology enrichment analysis on the significantly downregulated genes in hsa-miR-501-3p overexpression in cultured cells. Table S6. Gene Ontology enrichment analysis on the significantly upregulated genes in hsa-miR-501-3p overexpression in cultured cells. (XLS 172 kb
Additional file 1: Figure S1. of Serum microRNA miR-501-3p as a potential biomarker related to the progression of Alzheimer’s disease
This study’s definitions of patients with Alzheimer’s disease (AD) and controls on the basis of Braak staging in the ROW discovery set. (PDF 186 kb
Reduced CSF Water Influx in Alzheimer’s Disease Supporting the β-Amyloid Clearance Hypothesis
<div><p>Objective</p><p>To investigate whether water influx into cerebrospinal fluid (CSF) space is reduced in Alzheimer’s patients as previously shown in the transgenic mouse model for Alzheimer’s disease.</p><p>Methods</p><p>Ten normal young volunteers (young control, 21-30 years old), ten normal senior volunteers (senior control, 60-78 years old, MMSE ≥ 29), and ten Alzheimer’s disease (AD) patients (study group, 59-84 years old, MMSE: 13-19) participated in this study. All AD patients were diagnosed by neurologists specializing in dementia based on DSM-IV criteria. CSF dynamics were analyzed using positron emission tomography (PET) following an intravenous injection of 1,000 MBq [<sup>15</sup>O]H<sub>2</sub>O synthesized on-line.</p><p>Results</p><p>Water influx into CSF space in AD patients, expressed as influx ratio, (0.755 ± 0.089) was significantly reduced compared to young controls (1.357 ± 0.185; p < 0.001) and also compared to normal senior controls (0.981 ± 0.253, p < 0.05). Influx ratio in normal senior controls was significantly reduced compared to young controls (p < 0.01).</p><p>Conclusion</p><p>Water influx into the CSF is significantly reduced in AD patients. β-amyloid clearance has been shown to be dependent on interstitial flow and CSF production. The current study indicates that reduction in water influx into the CSF may disturb the clearance rate of β-amyloid, and therefore be linked to the pathogenesis of AD.</p><p>Trial Registration</p><p>UMIN Clinical Trials Registry <a href="https://upload.umin.ac.jp/cgi-open-bin/ctr/ctr.cgi?function=brows&action=brows&recptno=R000013940&type=summary&language=E" target="_blank">UMIN000011939</a></p></div
Schematic presentation of the results with mean (circle) and standard deviation (bar).
<p>Water influx into CSF space is expressed as influx ratio (IR): the ratio between the standardized uptake value (SUV, g/ml) of the ventricle to that of cortex. IR in Alzheimer’s disease patients (AD) is significantly reduced compared to both young controls (p < 0.001) and senior controls (p < 0.05), Mann-Whitney-Wilcoxon rank sum test. Note that there is no overlap in data points between AD and young controls. Reduction of influx ratio in senior controls compared to that in young control is found to be significant (p < 0.01) as well. A large range of influx ratio in senior controls suggests that the observed reduction likely represents one of the aging processes.</p
Consort Flow Diagram providing details of participant enrolment.
<p>Consort Flow Diagram providing details of participant enrolment.</p
Additional file 1 of Polygenic effects on the risk of Alzheimer’s disease in the Japanese population
Additional file 1: Figure S1. The excluded region around the APOE gene. We removed the APOE region, consisting of ±500 kb, from around the top-hit SNP rs1160985 (chr19:45403412) in our data. Each data point indicates GWAS p values from Jansen et al. [32] used as SNP weights in the PRS calculation. Figure S2. Associations between the PRS and covariates. Age at baseline examination and years of education were examined by Spearman correlation. Sex and doses of APOE ε4 and ε2 alleles were analysed by t tests or ANOVAs. CN = cognitively normal; MCI = mild cognitive impairment; ADD = Alzheimer's disease dementia. Figure S3. Associations between the PRS.adjLD and covariates. Age at examination and years of education were examined by Spearman correlations. Sex and dose of APOE ε4 and ε2 alleles were analysed by t tests or ANOVAs. Figure S4. Comparison of AD conversion between the APOE ε4 carriers and the APOE ε4 noncarriers with high PRS. Kaplan–Meier survival curves for conversion rates of MCI to AD in the APOE ε4 carriers and the APOE ε4 noncarriers with high PRS values. p-values were calculated by log-rank test. Figure S5. Age differences between the low- and high-PRS groups and between the nonconverters and converters. Baseline ages were compared between groups using the Wilcoxon rank-sum test. Each violin plot includes the kernel probability density of the data at different values and the box plots with the median value and the interquartile range
Data_Sheet_1_Decreased circulating branched-chain amino acids are associated with development of Alzheimer’s disease in elderly individuals with mild cognitive impairment.docx
BackgroundNutritional epidemiology has shown that inadequate dietary protein intake is associated with poor brain function in the elderly population. The plasma free amino acid (PFAA) profile reflects nutritional status and may have the potential to predict future changes in cognitive function. Here, we report the results of a 2-year interim analysis of a 3-year longitudinal study following mild cognitive impairment (MCI) participants.MethodIn a multicenter prospective cohort design, MCI participants were recruited, and fasting plasma samples were collected. Based on clinical assessment of cognitive function up to 2 years after blood collection, MCI participants were divided into two groups: remained with MCI or reverted to cognitively normal (“MCI-stable,” N = 87) and converted to Alzheimer’s disease (AD) (“AD-convert,” N = 68). The baseline PFAA profile was compared between the two groups. Stratified analysis based on apolipoprotein E ε4 (APOE ε4) allele possession was also conducted.ResultsPlasma concentrations of all nine essential amino acids (EAAs) were lower in the AD-convert group. Among EAAs, three branched-chain amino acids (BCAAs), valine, leucine and isoleucine, and histidine (His) exhibited significant differences even in the logistic regression model adjusted for potential confounding factors such as age, sex, body mass index (BMI), and APOE ε4 possession (p ConclusionThe PFAA profile, especially decreases in BCAAs and His, is associated with development of AD in MCI participants, and the difference was larger in the APOE ε4-negative population, suggesting that the PFAA profile is an independent risk indicator for AD development. Measuring the PFAA profile may have importance in assessing the risk of AD conversion in the MCI population, possibly reflecting nutritional status.Clinical trial registration[https://center6.umin.ac.jp/cgi-open-bin/ctr/ctr_view.cgi?recptno=R000025322], identifier [UMIN000021965].</p