The development of Alzheimer's disease (AD) biomarkers remains an unmet challenge, and new approaches that can improve current AD biomarker strategies are needed. Recent reports suggested that microRNA (miRNA) profiling of biological fluids has emerged as a diagnostic tool for several pathologic conditions. In this study, we measured six candidate miRNAs (miR-9, miR-29a, miR-29b, miR-34a, miR-125b, and miR-146a) in plasma and cerebrospinal fluid (CSF) of AD and normal subjects by using quantitative reverse transcriptase-polymerase chain reaction (qRT-PCR) to evaluate their potential usability as AD biomarkers. The qRT-PCR results showed that plasma miR-34a and miR-146a levels, and CSF miR-34a, miR-125b, and miR-146a levels in AD patients were significantly lower than in control subjects. On the other hand, CSF miR-29a and miR-29b levels were significantly higher than in control subjects. Our results provide a possibility that miRNAs detected in plasma and CSF can serve as biomarkers for AD.

mammalian sphingolipids is sphingosine ( trans -4-sphingenine, d18:1 4t ). Smaller amounts of other sphingoid bases, such as sphinganine (dihydrosphingosine, d18:0) and phytosphingosine (4-hydroxysphinganine, t18:0), are encountered frequently. In higher plants, the structures of sphingoid bases are more complicated than in mammals, because they can be desaturated at the C8-position by a ⌬ 8-sphingolipid desaturase, yielding cis -and trans -isomers of ⌬ 8-unsaturated sphingoid bases (d18:2 4t,8c(t) ) ( 3, 4 ). 9-Methyl-trans -4, trans -8-sphingadienine (d19:2 4t,8t ) is a typical structure found in yeasts ( 5 ). Sphingolipids of marine invertebrates have unique triene types of sphingoid bases with a conjugated diene such as 2-amino-4,8,10-octatriene-1, 3-diol (d18:3 4,8,10 ) and 2-amino-9-methyl-4,8,10-octatriene-1, 3-diol (d19:3 4,8,10 ) ( 6 ). Therefore, sphingolipids having various structures of sphingoid bases are ingested daily from foodstuffs ( 7-9 ).Dietary sphingolipids have gained attention for their potential to protect against infl ammation and cancers in the gut ( 10-13 ). One plausible mechanism for these effects may be via the hydrolysis of complex sphingolipids to bioactive ceramides and sphingosine, because those breakdown products are known to play important roles as intracellular mediators ( 14, 15 ). We previously demonstrated that dietary maize and yeast sphingolipids with sphingoid bases distinct from those of mammals are able to prevent the formation of aberrant crypt foci in 1,2-dimethylhydrazine-treated mice ( 16,17 ). We further showed that sphingoid bases prepared from various dietary sources can induce apoptosis in cancer cells (18)(19)(20).In early studies, Nilsson ( 21-23 ) investigated the digestion and intestinal absorption of sphingolipids containing sphingosine and sphinganine. Dietary sphingolipids can be hydrolyzed to their components, such as sphingoid bases, fatty acids, and the polar head group, by intestinal enzymes and are then taken up by mucosal cells ( 24,25 ). A large portion of sphingosine absorbed Sphingolipids are ubiquitous in all eukaryotic organisms and constitute a family of compounds that have a sphingoid base (long-chain base) with an amide-linked fatty acid and a polar head group. It is well known that there are diverse structures of sphingoid bases in nature ( Fig. 1 ) ( 1, 2 ). The most common sphingoid base of

Dysregulation of the gut microbiome is associated with several life-threatening conditions and thus might represent a useful target for the prevention of dementia. However, the relationship between the gut microbial population and dementia has not yet been fully clarified. We recruited outpatients visiting our memory clinic to participate in this study. Information on patient demographics, risk factors, and activities of daily living was collected, and cognitive function was assessed using neuropsychological tests and brain magnetic resonance imaging scans. Faecal samples were obtained, and the gut microbiome was assessed by terminal restriction fragment length polymorphism (T-RFLP) analysis, one of the most well-established and reliable 16S ribosomal RNA-based methods for classifying gut microbiota. Patients were divided into two groups, demented and non-demented. Multivariable logistic regression models were used to identify the variables independently associated with dementia. The T-RFLP analysis revealed differences in the composition of the gut microbiome: the number of Bacteroides (enterotype I) was lower and the number of ‘other’ bacteria (enterotype III) was higher in demented than non-demented patients. Multivariable analyses showed that the populations of enterotype I and enterotype III bacteria were strongly associated with dementia, independent of the traditional dementia biomarkers. Further studies of the metabolites of gut microbes are needed to determine the mechanism underlying this association.

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It was recently shown that administration of 1-deoxynojirimycin (DNJ) extracted from mulberry suppresses an increase in postprandial blood glucose in humans. These findings are of interest, but other physiological functions of DNJ are unknown. This study examined the effects of oral administration of DNJ (1 mg/kg of body weight/day) or mulberry extracts enriched in DNJ (meDNJ; 100 or 200 mg of extract/kg of body weight/day, equivalent to 0.53 or 1.06 mg of DNJ/kg of body weight/day) in male Sprague-Dawley rats for 4 weeks. DNJ and meDNJ enhanced expression of adiponectin mRNA in white adipose tissue; increased plasma adiponectin levels, enhanced expression of AMPK mRNA, activated the beta-oxidation system, and suppressed lipid accumulation in the liver. Intake of DNJ and meDNJ did not cause hepatic dysfunction and led to a reduction of oxidative stress. These results indicate the efficacy and safety of DNJ and meDNJ.

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