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.

Phospholipid hydroperoxides (PLOOH) accumulate abnormally in the erythrocytes of dementia patients, and dietary xanthophylls (polar carotenoids such as astaxanthin) are hypothesised to prevent the accumulation. In the present study, we conducted a randomised, double-blind, placebo-controlled human trial to assess the efficacy of 12-week astaxanthin supplementation (6 or 12 mg/d) on both astaxanthin and PLOOH levels in the erythrocytes of thirty middle-aged and senior subjects. After 12 weeks of treatment, erythrocyte astaxanthin concentrations were higher in both the 6 and 12 mg astaxanthin groups than in the placebo group. In contrast, erythrocyte PLOOH concentrations were lower in the astaxanthin groups than in the placebo group. In the plasma, somewhat lower PLOOH levels were found after astaxanthin treatment. These results suggest that astaxanthin supplementation results in improved erythrocyte antioxidant status and decreased PLOOH levels, which may contribute to the prevention of dementia. Key words: Astaxanthin: Phospholipid hydroperoxides: Erythrocytes: DementiaWe have previously confirmed that higher levels of phospholipid hydroperoxides (PLOOH), the primary oxidation products of phospholipids (PL) (1,2) , accumulate abnormally in the erythrocytes of dementia patients (3) . Such erythrocytes with high levels of lipid hydroperoxides have been postulated to have a decreased ability to transport oxygen to the brain, which may impair blood rheology, thus facilitating dementia (4 -8) . Recently, we have developed an HPLC method to determine erythrocyte carotenoid content (9) . Using this method, we gathered evidence that accumulation of polar oxygenated carotenoids (xanthophylls) occurs predominantly in human erythrocytes (9) , and that a decrease in xanthophylls and an increase in PLOOH levels in erythrocytes correlate with the severity of dementia (10) . These findings led to the hypothesis that xanthophyll supplementation may minimise the accumulation of erythrocyte PLOOH, and that xanthophylls could be used therapeutically as drugs or functional foods to prevent the disease. Although there is still scarce information on whether orally administered xanthophylls are distributed to human erythrocytes and actually inhibit erythrocyte PLOOH formation, our recent human study has revealed antioxidant properties of the xanthophyll lutein towards erythrocyte PLOOH formation (11) . Animal studies have also supported this hypothesis (12,13) .Among xanthophylls, astaxanthin has recently received attention for its potent antioxidant activity (14,15) . Astaxanthin is naturally synthesised by plants and algae, and is now commercially available as a food supplement from Haematococcus alga (16) . The recommended daily intake is estimated to be 1 -12 mg/d; however, there is not much information regarding the bioavailability of astaxanthin in humans. To the best of our knowledge, the occurrence and antioxidant roles of astaxanthin in human erythrocytes have not been reported.In this investigation of whether admini...

Amyloid β-peptide (Aβ) is hypothesized to play a key role by oxidatively impairing the capacity of red blood cells (RBCs) to deliver oxygen to the brain. These processes are implicated in the pathogenesis of Alzheimer's disease (AD). Although plasma Aβ has been investigated thoroughly, the presence and distribution of Aβ in human RBCs are still unclear. In this study, we quantitated Aβ40 and Aβ42 in human RBCs with ELISA assays, and provided evidence that significant amounts of Aβ could be detected in RBCs and that the RBC Aβ levels increased with aging. The RBC Aβ levels increased with aging. On the other hand, providing an antioxidant supplement (astaxanthin, a polar carotenoid) to humans was found to decrease RBC Aβ as well as oxidative stress marker levels. These results suggest that plasma Aβ40 and Aβ42 bind to RBCs (possibly with aging), implying a pathogenic role of RBC Aβ. Moreover, the data indicate that RBC Aβ40 and Aβ42 may constitute biomarkers of AD. As a preventive strategy, therapeutic application of astaxanthin as an Aβ-lowering agent in RBCs could be considered as a possible anti-dementia agent.Trial RegistrationControlled-Trials.com ISRCTN42483402

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Edited by Jesus AvilaKeywords: Erythrocyte Amyloid b-peptide Oxidative injury Phospholipid hydroperoxide Alzheimer's disease a b s t r a c tThe presence of amyloid b-peptide (Ab) in human blood has recently been established, and it has been hypothesized that Ab readily contacts red blood cells (RBC) and oxidatively impairs RBC functions. In this study, we conducted in vitro and in vivo studies, which provide evidence that Ab induces oxidative injury to RBC by binding to them, causing RBC phospholipid peroxidation and diminishing RBC endogenous carotenoids, especially xanthophylls. This type of damage is likely to injure the vasculature, potentially reducing oxygen delivery to the brain and facilitating Alzheimer's disease (AD). As a preventive strategy, because the Ab-induced RBC damage could be attenuated by treatment of RBC with xanthophylls, we suggest that xanthophylls may contribute to the prevention of AD.