Zinc Overload Enhances APP Cleavage and Aβ Deposition in the Alzheimer Mouse Brain

BACKGROUND: Abnormal zinc homeostasis is involved in β-amyloid (Aβ) plaque formation and, therefore, the zinc load is a contributing factor in Alzheimer's disease (AD). However, the involvement of zinc in amyloid precursor protein (APP) processing and Aβ deposition has not been well established in AD animal models in vivo. METHODOLOGY/PRINCIPAL FINDINGS: In the present study, APP and presenilin 1 (PS1) double transgenic mice were treated with a high dose of zinc (20 mg/ml ZnSO4 in drinking water). This zinc treatment increased APP expression, enhanced amyloidogenic APP cleavage and Aβ deposition, and impaired spatial learning and memory in the transgenic mice. We further examined the effects of zinc overload on APP processing in SHSY-5Y cells overexpressing human APPsw. The zinc enhancement of APP expression and cleavage was further confirmed in vitro. CONCLUSIONS/SIGNIFICANCE: The present data indicate that excess zinc exposure could be a risk factor for AD pathological processes, and alteration of zinc homeostasis is a potential strategy for the prevention and treatment of AD

Risk factors for early colonization of mutans streptococci - a multiple logistic regression analysis in Swedish 1-year-olds

Background: Mutans streptococci (MS) are closely related to the development of dental caries and are usually established in the oral cavity during early childhood. The aim of the study was to identify factors associated with the presence of MS in Swedish 1-year-olds. Methods: Parents completed a questionnaire on different caries-associated factors and an oral bacterial sample was collected from 1,050 (526 boys, 524 girls) 1-year-olds. Multiple logistic regression analyses were performed to identify risk factors for colonization with MS. Results: MS were found in 27% of the 1-year-olds with teeth. High or very high MS scores (2-3) were found in 72 (7%) of the children. MS score was correlated to the number of erupted teeth (p less than 0.001). No difference due to gender was found. Multiple logistic regression analysis showed that presence of bacteria was associated with: caries in a sibling, other beverages than water between meals, and more than 8 erupted teeth. High or very high MS scores (2-3) were associated with other beverages than water between meals, and more than 8 erupted teeth. Conclusions: Number of teeth present, diet and family aspects were factors associated with presence of MS in 1-year-olds. To develop high or very high MS scores, the number of erupted teeth and dietary habits are important.Funding Agencies|Public Dental Service/Folktandvarden Ostergotland, Sweden</p