Combined assessment of DYRK1A, BDNF and homocysteine levels as diagnostic marker for Alzheimer’s disease

Early identification of Alzheimer’s disease (AD) risk factors would aid development of interventions to delay the onset of dementia, but current biomarkers are invasive and/or costly to assess. Validated plasma biomarkers would circumvent these challenges. We previously identified the kinase DYRK1A in plasma. To validate DYRK1A as a biomarker for AD diagnosis, we assessed the levels of DYRK1A and the related markers brain-derived neurotrophic factor (BDNF) and homocysteine in two unrelated AD patient cohorts with age-matched controls. Receiver-operating characteristic curves and logistic regression analyses showed that combined assessment of DYRK1A, BDNF and homocysteine has a sensitivity of 0.952, a specificity of 0.889 and an accuracy of 0.933 in testing for AD. The blood levels of these markers provide a diagnosis assessment profile. Combined assessment of these three markers outperforms most of the previous markers and could become a useful substitute to the current panel of AD biomarkers. These results associate a decreased level of DYRK1A with AD and challenge the use of DYRK1A inhibitors in peripheral tissues as treatment. These measures will be useful for diagnosis purposes.This work was supported by the FEANS. We acknowledge the platform accommodation and animal testing of the animal facility at the Institute Jacques-Monod (University Paris Diderot) and the FlexStation3 facility of the Functional and Adaptive Biology (BFA) LaboratoryPeer reviewe

Prions in Milk from Ewes Incubating Natural Scrapie

Since prion infectivity had never been reported in milk, dairy products originating from transmissible spongiform encephalopathy (TSE)-affected ruminant flocks currently enter unrestricted into the animal and human food chain. However, a recently published study brought the first evidence of the presence of prions in mammary secretions from scrapie-affected ewes. Here we report the detection of consistent levels of infectivity in colostrum and milk from sheep incubating natural scrapie, several months prior to clinical onset. Additionally, abnormal PrP was detected, by immunohistochemistry and PET blot, in lacteal ducts and mammary acini. This PrPSc accumulation was detected only in ewes harbouring mammary ectopic lymphoid follicles that developed consequent to Maedi lentivirus infection. However, bioassay revealed that prion infectivity was present in milk and colostrum, not only from ewes with such lympho-proliferative chronic mastitis, but also from those displaying lesion-free mammary glands. In milk and colostrum, infectivity could be recovered in the cellular, cream, and casein-whey fractions. In our samples, using a Tg 338 mouse model, the highest per ml infectious titre measured was found to be equivalent to that contained in 6 µg of a posterior brain stem from a terminally scrapie-affected ewe. These findings indicate that both colostrum and milk from small ruminants incubating TSE could contribute to the animal TSE transmission process, either directly or through the presence of milk-derived material in animal feedstuffs. It also raises some concern with regard to the risk to humans of TSE exposure associated with milk products from ovine and other TSE-susceptible dairy species

Peanut allergens are rapidly transferred in human breast milk and can prevent sensitization in mice

International audienceBackground: Food allergens have been evidenced in breast milk under physiological conditions, but the kinetic and the role of this passage in food allergies are still unclear. We then aimed to analyze the passage of peanut allergens in human breast milk and their allergenicity/immunomodulatory properties. Methods: Human breast milk was collected from two non-atopic peanut-tolerant mothers before and at different time points after ingestion of 30 g of commercial roasted peanut. Ara h 6, Ara h 6 immune complexes, and the IgE binding capacity of breast milk samples were measured using specific immunoassays. Their allergenic functionality was then assessed using cell-based assay. Finally, human breast milk obtained before or after peanut ingestion was administered intragastrically to BALB/c mice at different ages, and mice were further experimentally sensitized to peanut using cholera toxin. Results: Ara h 6 is detected as soon as 10 min after peanut ingestion, with peak values observed within the first hour after ingestion. The transfer is long-lasting, small quantities of peanut allergens being detected over a 24-h period. IgG-Ara h 6 and IgA-Ara h 6 immune complexes are evidenced, following a different kinetic of excretion than free allergens. Peanut allergens transferred in milk are IgE reactive and can induce an allergic reaction in vitro. However, administration of human breast milk to young mice, notably before weaning, does not lead to sensitization, but instead to partial oral tolerance. Conclusion: The low quantities of immunologically active allergens transferred through breast milk may prevent instead of priming allergic sensitization to peanut

Staphylococcal Enterotoxin Gene Cluster: Prediction of Enterotoxin (SEG and SEI) Production and of the Source of Food Poisoning on the Basis of v Saβ Typing

International audienceCurrently, only 5 (SEA to SEE) out of 27 known staphylococcal enterotoxins can be analyzed using commercially available kits. Six genes (seg, sei, sem, sen, seo, and seu), encoding putative and undetectable enterotoxins, are located on the enterotoxin gene cluster (egc), which is part of the Staphylococcus aureus genomic island vSa beta. These enterotoxins have been described as likely being involved in staphylococcal food-poisoning outbreaks. The aim of the present study was to determine if whole-genome data can be used for the prediction of staphylococcal egc enterotoxin production, particularly enterotoxin G (SEG) and enterotoxin I (SEI). For this purpose, whole-genome sequences of 75 Staphylococcus aureus strains from different origins (food-poisoning outbreaks, human, and animal) were investigated by applying bioinformatics methods (phylogenetic analysis using the core genome and different alignments). SEG and SEI expression was tested in vitro using a sandwich enzyme-linked immunosorbent assay method. Strains could be allocated to 14 different vSa beta types, each type being associated with a single clonal complex (CC). In addition, the vSa beta type and CC were associated with the origin of the strain (human or cattle derived). The amount of SEG and SEI produced also correlated with the vSa beta type and the CC of a strain. The present results show promising indications that the in vitro production of SEG and SEI can be predicted based on the vSa beta type or CC of a strain.IMPORTANCE Besides having infectious properties in human and animals, S. aureus can produce different enterotoxins in food. The enterotoxins can cause vomiting and diarrhea, often involving many people. Most of these outbreaks remain undiscovered, as detection methods for enterotoxins are only available for a few enterotoxins but not for the more recently discovered enterotoxins G (SEG) and I (SEI). In this study, we show promising results that in vitro production of SEG and SEI can be predicted based on the whole-genome sequencing data of a strain. In addition, these data could be used to find the source (human or cattle derived) of an outbreak strain, which is the key for a better understanding of the role SEG and SEI play in foodborne outbreaks caused by S. aureus