Fibrillar Aβ (beta) triggers microglial proteome alterations and dysfunction in Alzheimer mouse models

Microglial dysfunction is a key pathological feature of Alzheimer's disease (AD), but little is known about proteome-wide changes in microglia during the course of AD and their functional consequences. Here, we performed an in-depth and time-resolved proteomic characterization of microglia in two mouse models of amyloid beta (A beta) pathology, the overexpression APPPS1 and the knock-in APP-NL-G-F (APP-KI) model. We identified a large panel of Microglial A beta Response Proteins (MARPs) that reflect heterogeneity of microglial alterations during early, middle and advanced stages of A beta deposition and occur earlier in the APPPS1 mice. Strikingly, the kinetic differences in proteomic profiles correlated with the presence of fibrillar A beta, rather than dystrophic neurites, suggesting that fibrillar A beta may trigger the AD-associated microglial phenotype and the observed functional decline. The identified microglial proteomic fingerprints of AD provide a valuable resource for functional studies of novel molecular targets and potential biomarkers for monitoring AD progression or therapeutic efficacy

Profile of European adults interested in internet-based personalized nutrition: The Food4Me Study

Purpose Personalised intervention may have greater potential for reducing the global burden of non-communicable diseases and for promoting better health and wellbeing across the life-span than the conventional “one size fits all” approach. However, the characteristics of individuals interested in personalised nutrition (PN) are unclear. Therefore, the aim of this study was to describe the characteristics of European adults interested in taking part in an internet-based PN study. Methods Individuals from seven European countries (UK, Ireland, Germany, the Netherlands, Spain, Greece and Poland) were invited to participate in the study via the Food4Me website (http://www.food4me.org). Two screening questionnaires were used to collect data on socio-demographic, anthropometric and health characteristics as well as dietary intakes. Results A total of 5662 individuals expressed an interest in the study (mean age 40 ± 12.7; range 15-87 years). Of these 64.6% were female and 96.9% were Caucasian. Overall, 12.9% were smokers and 46.8% reported the presence of a clinically diagnosed disease. Furthermore, 46.9% were overweight or obese and 34.9% were sedentary during leisure time. Assessment of dietary intakes showed that 54.3% of individuals reported consuming at least 5 portions of fruit and vegetables per day, 45.9% consumed more than 3 servings of wholegrains and 37.2% limited their salt intake to less than 5.75g per day. Conclusions Our data indicate that individuals volunteering to participate in an internet-based PN study are broadly representative of the European adult population, most of whom had adequate nutrient intakes but who could benefit from improved dietary choices and greater physical activity. Future use of internet-based PN approaches is thus relevant to a wide target audience

Using canned explanations within a mobile context engine

Mobile applications have to adhere to many constraints. ContextEngine has been developed for the Android platform to easier deal with such limitations and situation-specific information across applications to, thus, create context-aware, mobile systems. With the increased adaptability and dynamics of context-aware applications comes an increase complexity, which in turn makes it harder to understand the behaviour of such applications. In this paper we describe how we enhanced the ContextEngine platform with explanation capabilities. Explaining can be seen as complex reasoning task on its own. Here, we focus on “canned explanations”. Canned explanations are information artefacts, pre-formulated by the software engineer, that serve as explanatory artefacts stored in the system and delivered to the user on demand

Beneficial Effect of ACI-24 Vaccination on Aβ Plaque Pathology and Microglial Phenotypes in an Amyloidosis Mouse Model

Amyloid-β (Aβ) deposition is an initiating factor in Alzheimer’s disease (AD). Microglia are the brain immune cells that surround and phagocytose Aβ plaques, but their phagocytic capacity declines in AD. This is in agreement with studies that associate AD risk loci with genes regulating the phagocytic function of immune cells. Immunotherapies are currently pursued as strategies against AD and there are increased efforts to understand the role of the immune system in ameliorating AD pathology. Here, we evaluated the effect of the Aβ targeting ACI-24 vaccine in reducing AD pathology in an amyloidosis mouse model. ACI-24 vaccination elicited a robust and sustained antibody response in APPPS1 mice with an accompanying reduction of Aβ plaque load, Aβ plaque-associated ApoE and dystrophic neurites as compared to non-vaccinated controls. Furthermore, an increased number of NLRP3-positive plaque-associated microglia was observed following ACI-24 vaccination. In contrast to this local microglial activation at Aβ plaques, we observed a more ramified morphology of Aβ plaque-distant microglia compared to non-vaccinated controls. Accordingly, bulk transcriptomic analysis revealed a trend towards the reduced expression of several disease-associated microglia (DAM) signatures that is in line with the reduced Aβ plaque load triggered by ACI-24 vaccination. Our study demonstrates that administration of the Aβ targeting vaccine ACI-24 reduces AD pathology, suggesting its use as a safe and cost-effective AD therapeutic intervention

Additional file 2 of Breast cancer risks associated with missense variants in breast cancer susceptibility genes

Additional file 2