ABSTRACT
The abnormal assembly of tau protein in neurons is the pathological hallmark of multiple neurodegenerative diseases, including Alzheimer's disease (AD). In addition, assembled tau associates with extracellular vesicles (EVs) in the central nervous system of patients with AD, which is linked to its clearance and prion-like propagation between neurons. However, the identities of the assembled tau species and the EVs, as well as how they associate, are not known. Here, we combined quantitative mass spectrometry, cryo-electron tomography and single-particle cryo-electron microscopy to study brain EVs from AD patients. We found filaments of truncated tau enclosed within EVs enriched in endo-lysosomal proteins. We observed multiple filament interactions, including with molecules that tethered filaments to the EV limiting membrane, suggesting selective packaging. Our findings will guide studies into the molecular mechanisms of EV-mediated secretion of assembled tau and inform the targeting of EV-associated tau as potential therapeutic and biomarker strategies for AD.
ABSTRACT
INTRODUCTION: Intestinal parasitoses are very common infections in tropical areas. By contrast, they are rarely diagnosed in developed countries, and are mostly seen in specific populations. PATIENTS AND METHODS: This analytical observational study was longitudinally performed in a French university hospital (2007-2011). It dealt with the study of gastrointestinal carriage of parasites in internationally adopted children. A standard stool examination was therefore systematically undertaken for every new immigrant. Association with risk factors was made by uni- and multivariate analysis. RESULTS: Overall, 69 stool samples were analyzed. The proportion of positive samples was 78 %. Protozoans, mainly Giardia duodenalis, were more prevalent than helminths. In univariate analysis, a subject's low weight and height were significantly associated with intestinal parasite carriage. Amoebae were more frequent in older children and in children from Haiti, as confirmed by the trend observed in the multivariate analysis. Flagellates were seen more often in African children. Infections with multiple parasite species were observed in half of the study population, and were inversely correlated to increasing age. DISCUSSION: According to the results of this study, gastrointestinal parasites are still very frequent in stool samples from immigrant children. Since they are easy to transmit, the majority of infections were protozoan. The best antiparasitic strategy lies in: (a) the routine screening of stool from any immigrant child coming from endemic areas and (b) the use of antiparasitic treatment.
