Bárbara Rita Cardoso

Nutritional status of selenium in Alzheimer's disease patients

Studies have shown that various antioxidants are decreased in different age-related degenerative diseases and thus, oxidative stress would have a central role in the pathogenesis of many disorders that involve neuronal degeneration, including Alzheimers disease (AD). The present study aimed to assess the nutritional status of Se in AD patients and to compare with control subjects with normal cognitive function. The case-control study was carried out on a group of elderly with AD (n 28) and compared with a control group (n 29), both aged between 60 and 89 years. Se intake was evaluated by using a 3-d dietary food record. Se was evaluated in plasma, erythrocytes and nails by using the method of hydride generation atomic absorption spectroscopy. Deficient Se intake was largely observed in the AD group. AD patients showed significantly lower Se levels in plasma, erythrocytes and nails (32.59 microg/l, 43.74 microg/l and 0.302 microg/g) when compared with the control group (50.99 microg/l, 79.16 microg/l and 0.400 microg/g). The results allowed us to suggest that AD has an important relation with Se deficiency.

Selenium status in elderly: Relation to cognitive decline

Studies show that decreased antioxidant system is related to cognitive decline. Thus we aimed to measure selenium (Se) status in Alzheimers disease (AD) and mild cognitive impairment (MCI) elderly and compared them with a control group (CG). 27 AD, 17 MCI and 28 control elderly were evaluated. Se concentration was determined in plasma and erythrocyte by using hydride generation atomic absorption spectroscopy. Erythrocyte Se concentration in AD group was lower than CG (43.73±23.02μg/L and 79.15±46.37μg/L; p=0.001), but not statistically different from MCI group (63.97±18.26μg/L; p=0.156). AD group exhibited the lowest plasma Se level (34.49±19.94μg/L) when compared to MCI (61.36±16.08μg/L; p=0.000) and to CG (50.99±21.06μg/L; p=0.010). It is observed that erythrocyte Se decreases as cognition function does. Since erythrocyte reflects longer-term nutritional status, the data point to the importance of the relation between Se exposure and cognitive function. Our findings suggest that the deficiency of Se may contribute to cognitive decline among aging people.

Importance and management of micronutrient deficiencies in patients with Alzheimer's disease.

Alzheimer’s disease (AD) is the most common form of dementia, and it generally affects the elderly. It has been suggested that diet is an intensively modifiable lifestyle factor that might reduce the risk of AD. Because epidemiological studies generally report the potential neuronal protective effects of various micronutrients, the aim of this study was to perform a literature review on the major nutrients that are related to AD, including selenium, vitamins C and E, transition metals, vitamin D, B-complex vitamins, and omega-3 fatty acids.

Glutathione peroxidase 4: a new player in neurodegeneration?

Glutathione peroxidase 4 (GPx4) is an antioxidant enzyme reported as an inhibitor of ferroptosis, a recently discovered non-apoptotic form of cell death. This pathway was initially described in cancer cells and has since been identified in hippocampal and renal cells. In this Perspective, we propose that inhibition of ferroptosis by GPx4 provides protective mechanisms against neurodegeneration. In addition, we suggest that selenium deficiency enhances susceptibility to ferroptotic processes, as well as other programmed cell death pathways due to a reduction in GPx4 activity. We review recent studies of GPx4 with an emphasis on neuronal protection, and discuss the relevance of selenium levels on its enzymatic activity.

Selenium status and hair mercury levels in riverine children from Rondônia, Amazonia

OBJECTIVE Riverine communities in Rondônia State are exposed to high selenium (Se) content in their diet because of the high-selenium soils identified in the Amazon. However, the Amazonian population has a high mercury (Hg) exposure because this metal accumulates in the soil. Because children are more vulnerable to Hg toxicity, the aim of this study was to evaluate and correlate Se status and hair Hg levels in riverine children (aged 3-9 y) living in two different locations in Rondônia State: Demarcação area (DA) and Gleba do Rio Preto (GRP). METHODS Se levels were assessed using hydride generation quartz tube atomic absorption spectroscopy; total hair Hg levels were assessed using cold vapor atomic absorption spectrometry. Dietary intake was evaluated through a 24-h food record and a food frequency questionnaire. RESULTS Forty-two children participated in this study. Eighty-four percent of the children from DA showed low plasma Se. Conversely, all children from GRP presented plasma Se levels above the reference values. Forty-five percent of the children from DA presented low erythrocyte levels, and 55% of the children from GRP showed concentration in erythrocyte above the reference values. The mean Se intake was 41.8 μg/d in DA and 179.0 μg/d in GRP. High hair Hg levels were observed in children from both the DA and GRP (3.57 ± 1.86 and 6.24 ± 5.89, respectively). CONCLUSIONS Children from both riverine communities are likely to present altered Se status according to their dietary intake. Additionally, these children are highly exposed to Hg, mainly through fish consumption, and the toxicity of this metal may cause metabolic damage.

Excessive early-life dietary exposure: a potential source of elevated brain iron and a risk factor for Parkinson's disease

Iron accumulates gradually in the ageing brain. In Parkinson’s disease, iron deposition within the substantia nigra is further increased, contributing to a heightened pro-oxidant environment in dopaminergic neurons. We hypothesise that individuals in high-income countries, where cereals and infant formulae have historically been fortified with iron, experience increased early-life iron exposure that predisposes them to age-related iron accumulation in the brain. Combined with genetic factors that limit iron regulatory capacity and/or dopamine metabolism, this may increase the risk of Parkinson’s diseases. We propose to (a) validate a retrospective biomarker of iron exposure in children; (b) translate this biomarker to adults; (c) integrate it with in vivo brain iron in Parkinson’s disease; and (d) longitudinally examine the relationships between early-life iron exposure and metabolism, brain iron deposition and Parkinson’s disease risk. This approach will provide empirical evidence to support therapeutically addressing brain iron deposition in Parkinson’s diseases and produce a potential biomarker of Parkinson’s disease risk in preclinical individuals.

Glutathione Peroxidase 1 Pro198Leu Polymorphism in Brazilian Alzheimer's Disease Patients: Relations to the Enzyme Activity and to Selenium Status

Background/Aims: Oxidative stress plays a central role in Alzheimer’s disease (AD). Pro198Leu cytosolic glutathione peroxidase (GPx1) polymorphism seems to be associated with a lower activity of this enzyme, but there are no studies with AD patients. Thus, the aim was to determine the frequency of the GPx1 Pro198Leu polymorphism in AD patients and to verify its relation to glutathione peroxidase (GPx) activity and selenium (Se) status. Methods: The study was carried out in a group of AD elderly (n = 28) compared to a control group (n = 29). Blood Se concentrations were measured through hydride generation atomic absorption spectroscopy. GPx activity was determined using a commercial kit, and the polymorphism using amplified DNA sequencing. Results: The distribution of genotypes was not different between groups. The variant allele frequency was 0.179 (AD group) and 0.207 (control group). Although no differences regarding GPx activity were found between individuals with different genotypes, lower blood Se levels were found in Pro/Pro AD patients compared to Pro/Pro control subjects, which was not found in the Pro/Leu groups. Moreover, the association between the erythrocyte Se concentration and GPx activity was affected by the Pro198Leu genotype. Conclusions: Results indicate that this polymorphism had apparently affected Se status in AD patients and that more studies in this field are necessary.

Selenium Levels in Serum, Red Blood Cells, and Cerebrospinal Fluid of Alzheimer’s Disease Patients: A Report from the Australian Imaging, Biomarker & Lifestyle Flagship Study of Ageing (AIBL)

Selenium (Se) protects cells against oxidative stress damage through a range of bioactive selenoproteins. Increased oxidative stress is a prominent feature of Alzheimers disease (AD), and previous studies have shown that Se deficiency is associated with age-related cognitive decline. In this study, we assessed Se status in different biofluids from a subgroup of participants in the Australian Imaging, Biomarkers and Lifestyle Flagship Study of Ageing. As Se in humans can either be an active component of selenoproteins or inactive via non-specific incorporation into other proteins, we used both size exclusion chromatography-inductively coupled plasma-mass spectrometry (SEC-ICP-MS) and tandem mass spectrometry to characterize selenoproteins in serum. We observed no differences in total Se concentration in serum or cerebrospinal fluid of AD subjects compared to mildly cognitively impairment patients and healthy controls. However, Se levels in erythrocytes were decreased in AD compared to controls. SEC-ICP-MS analysis revealed a dominant Se-containing fraction. This fraction was subjected to standard protein purification and a bottom-up proteomics approach to confirm that the abundant Se in the fraction was due, in part, to selenoprotein P. The lack of change in the Se level is at odds with our previous observations in a Brazilian population deficient in Se, and we attribute this to the Australian cohort being Se-replete.

The APOE ε4 Allele Is Associated with Lower Selenium Levels in the Brain: Implications for Alzheimer’s Disease

The antioxidant activity of selenium, which is mainly conferred by its incorporation into dedicated selenoproteins, has been suggested as a possible neuroprotective approach for mitigating neuronal loss in Alzheimers disease. However, there is inconsistent information with respect to selenium levels in the Alzheimers disease brain. We examined the concentration and cellular compartmentalization of selenium in the temporal cortex of Alzheimers disease and control brain tissue. We found that Alzheimers disease was associated with decreased selenium concentration in both soluble (i.e., cytosolic) and insoluble (i.e., plaques and tangles) fractions of brain homogenates. The presence of the APOE ε4 allele correlated with lower total selenium levels in the temporal cortex and a higher concentration of soluble selenium. Additionally, we found that age significantly contributed to lower selenium concentrations in the peripheral membrane-bound and vesicular fractions. Our findings suggest a relevant interaction between APOE ε4 and selenium delivery into brain, and show changes in cellular selenium distribution in the Alzheimers disease brain.

Brazil nuts: Nutritional composition, health benefits and safety aspects

Brazil nuts are among the richest selenium food sources, and studies have considered this Amazonian nut as an alternative for selenium supplementation. Besides selenium, Brazil nuts present relevant content of other micronutrients such as magnesium, copper, and zinc. The nutritional composition of nuts, also characterized by adequate fatty acid profile and high content of protein and bioactive compounds, has many health benefits. In the present review, we examine the nutritional composition of Brazil nuts, comparing it with other nuts, and describe the relevance of possible contaminants and metal toxicants observed in this nut for human health. Furthermore, we report different trials available in the literature, which demonstrate positive outcomes such as modulation of the lipid serum profile, enhancement of the antioxidant system and improvement of anti-inflammatory response. These effects have been assessed under different conditions, such as cognitive impairment, dyslipidemia, cancer, and renal failure.