Oxidative stress constitutes a hallmark of Alzheimer's disease (AD). Recent studies also point to redox active metals such as iron, copper and zinc in mediating oxidative stress in AD pathogenesis. However, the reactivity of cerebrospinal fluid (CSF) iron and its possible correlation with the severity of cognitive decline in both Alzheimer's patients and subjects with mild cognitive impairment (MCI) is still unknown. Here we show that different stages of cognitive and functional impairment are associated with changes in CSF reactive iron. In this work, we compared CSF samples from 56 elders, classified into 4 groups according to their scores on the Clinical Dementia Rating scale (CDR). Total CSF iron was analyzed by atomic absorption spectrometry. Redox-active iron was analyzed by a novel fluorimetric assay. One-way ANOVA was used to test differences in mean values, and Newman-Keuls Multiple Comparison Test was used for multi group comparisons. No difference in total CSF iron was found between different groups. Significant amounts of redox-active iron were found in CSF and their levels correlated with the extent of cognitive impairment. Redox-active CSF iron levels increased with the degree of cognitive impairment from normal to MCI subjects, while AD patients showed an abrupt decrease to levels close to zero. Given the relevance of oxidative damage in neurodegeneration, it might be possible to associate the development of cognitive and functional decline with the presence of redox-active iron in the CSF. The decrease in redox-active iron found in AD patients may represent a terminal situation, whereby the central nervous system attempts to minimize iron-associated toxicity.

No abstract

Objectives Choline is a critical nutrient for fetal development. Pregnancy studies showed that most women have choline intakes below the adequate intake (AI) level of 450 mg/d. Research on plasma free choline as an indicator of dietary choline intake showed conflicting results to date. We sought to compare plasma free choline concentration between women with different choline intakes and to explore the association between plasma free choline and dietary choline intake in early (EP) and late pregnancy (LP). Methods This study included data and non-fasting plasma samples from pregnant women enrolled in the Alberta Pregnancy Outcomes and Nutrition (APrON) cohort study. EP (<20 weeks of gestation) and LP (>20 weeks of gestation) dietary choline intake was estimated using a 24-hr recall. Two categories of dietary choline intake were created: 1) low choline (LCI), i.e., choline intake in 1st quartile (Q) in EP, with these women having choline intake in 1st or 2nd Q in LP (n = 61); 2) high choline intake (HCI), i.e., choline intake in 4th Q in EP and in 3rd or 4th Q in LP (n = 46). Linear mixed-effects models were used to explore the association between plasma free choline and dietary choline intake across EP and LP, after adjustment for maternal age, ethnicity and weeks of gestation. Results Median (IQR) maternal age was 32 (30–35) y, and 80% were Caucasian. LCI was 101 (86–109) and 109 (93–127) mg/day in EP and LP, respectively, and HCI was 251 (223–286) and 212 (177–274) mg/day. Plasma free choline (μmol/L) did not differ between LCI and HCI at EP [LCI: 10.6 (9.03, 12.9); HCI: 11.7 (10.2, 13.8)] and LP [LCI: 11.7 (10.6, 12.7); HCI: 12.7 (10.7, 15.8)] (P > 0.05, Wilcoxon rank-sum test). Per 10 mg of choline intake, plasma free choline increased by 0.34 (95%CI 0.12, 0.56) in those with LCI, and 0.18 (95%CI 0.050, 0.31) in women with HCI, across EP and LP after adjustment. Conclusions In this subgroup of pregnant women, plasma free choline concentration did not reflect differences in dietary choline intake in EP or LP. This may be explained by an overall low choline intake (<AI) which would promote rapid tissue uptake of choline. The identification of a sensitive and dynamic biomarker for choline status is required. Funding Sources UBC Four Year Doctoral Fellowship, Canada Research Chair Program, CIHR NTE Grant FRN 160,942, Alberta Innovates for the APrON cohort.