Background Early-life lead (Pb) exposure induces overexpression of the amyloid beta precursor protein and its amyloid beta product in older rats and primates. We exposed rodents to Pb during different life span periods and examined cognitive function in old age and its impact on biomarkers associated with Alzheimer’s disease (AD). Methods Morris, Y, and the elevated plus mazes were used. Western blot, quantitative polymerase chain reaction (qPCR), and enzyme-linked immunosorbent assay were used to study the levels of AD biomarkers. Results Cognitive impairment was observed in mice exposed as infants but not as adults. Overexpression of AD-related genes (amyloid beta precursor protein and β-site amyloid precursor protein cleaving enzyme 1) and their products, as well as their transcriptional regulator—specificity protein 1 (Sp1)—occurred only in older mice with developmental exposure to Pb. Conclusions A window of vulnerability to Pb neurotoxicity exists in the developing brain that can influence AD pathogenesis and cognitive decline in old age.

BackgroundCaffeine containing energy drinks (EDs) are heavily consumed, particularly among young adults. The number of reports of caffeine intoxication from caffeinated EDs and problems related to caffeine dependence and withdrawal is increasing. The objective was to assess the knowledge and perceived beneficial effects of EDs consumers, to assess consumption patterns and determine the adverse effects experienced by different EDs consumer groups residing in Saudi Arabia.MethodsAn observational cross-sectional study with data from a randomly selected Saudi population was conducted during the period of January 15th, 2015, to April 15th, 2015, using a pre-tested 43-item questionnaire. The data were obtained and collected using interview questionnaires. Sociodemographic characteristics and data on EDs consumption patterns, the level of awareness among study subjects, and the purported benefits and reported adverse effects of EDs were collected. Frequency, percentage, and arithmetic means were calculated using Chi-square and ANOVA tests, and data with p < 0.05 were considered significant.ResultsOf the 816 individuals invited to participate in the study, 783 participants responded and completed interviews, response rate was 96%. Consumers attributed the popularity of EDs to massive advertising media (46.7%) and their stimulating and invigorating effects (37.5%). EDs are consumed by subjects for their effects on fatigue reduction (64.6%), increased alertness and focus (75.8%), and assistance during long driving trips (75.7%). Study subjects reported suffering from adverse effects, including mainly diuresis (53.7%), palpitations (50.7%), insomnia (50.7%). Importantly, an inverse association was identified between knowledge of EDs and consumption rate, and a proportional association was identified between experienced adverse effects and consumption frequency. Lower knowledge scores were identified in daily consumers than in 1–3 times monthly consumers; higher adverse events were experienced by daily consumers than by 1–3 times monthly consumers. The majority of consumers (84.6%) recommended that authorities should regulate EDs consumption.ConclusionsExcessive EDs consumption is associated with an increased risk of experiencing several adverse events, which is commensurate with published studies. Increasing knowledge about EDs and their possible risks could decrease their consumption by the general public.

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Tolfenamic acid lowers the levels of the amyloid precursor protein (APP) and amyloid beta (Aβ) when administered to C57BL/6 mice by lowering their transcriptional regulator specificity protein 1 (SP1). To determine whether changes upstream in the amyloidogenic pathway that forms Aβ plaques would improve cognitive outcomes, we administered tolfenamic acid for 34 days to hemizygous R1.40 transgenic mice. Following the characterization of cognitive deficits in these mice, assessment of spatial learning and memory functions revealed that treatment with tolfenamic acid attenuated long-term memory and working memory deficits, determined using Morris water maze (MWM) and the Y-maze. These improvements occurred within a shorter period of exposure than that seen with clinically approved drugs. Cognitive enhancement was accompanied by reduction in the levels of the SP1 protein (but not mRNA), followed by lowering both the mRNA and protein levels of APP, and subsequent Aβ levels. These findings provide evidence that tolfenamic acid can disrupt the pathological processes associated with AD and are relevant to its scheduled biomarker study in AD patients.

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