Brain Selenium in Alzheimer’s Disease (BRAIN SEAD Study): a Systematic Review and Meta-Analysis

Abstract

Oxidative stress has been found to be implicated in the development of Alzheimer's disease (AD). In this meta-analytic review, we compared tissue levels between AD and non-AD brains of selenium, an important biological trace element well known for its vital role in the brain function. We included 14 studies with 40 observations on selenium concentrations in AD and control brains. The effect size as standardized mean difference (SMD) was generated using review manager 5.3. Random-effects meta-analysis indicated a decrease (SMD = - 0.42) in brain tissue selenium levels in AD as compared to non-AD controls. The subgroup meta-analysis demonstrated that the selenium levels were decreased in the temporal, hippocampal, and cortex regions in AD. The funnel plot with Egger's (p = 0.88) and Begg's tests (p = 0.24) detected no significant publication bias. The results of sensitivity analysis indicated that no single study/observation had significantly influenced the overall outcome. This meta-analysis provides consolidated evidence for a significant decrease of selenium status in AD brains compared to controls. In line with the evidence supporting selenium's antioxidant role and the involvement of oxidative stress in AD development, this meta-analysis supports new therapeutic strategies aimed at brain tissue selenium homeostasis in AD.

Spotlight on Ferroptosis: Iron-Dependent Cell Death in Alzheimer’s Disease

“…Selenium is decreased in the hippocampal, temporal, and cortical regions in AD, consistent with attenuated antioxidant capacity and augmented oxidative stress (Varikasuvu et al, 2019 ). Selenium, as selenocysteine, is essential for GPX4 synthesis.…”

Whole transcriptomein-silicoscreening implicates cardiovascular and infectious disease in the mechanism of action underlying atypical antipsychotic side-effects

“…Our findings bring greater clarity to this previous work by providing evidence that antipsychotics directly act on selenium pathways. This has particular relevance to neurodegeneration where selenium deficiency in Alzheimer’s disease brain tissue has been observed and is hypothesised to play a role in cardiovascular side effects in Parkinson’s disease [30,31]. Our findings provide a clear indication for prioritising study of selenium deficiency and its interaction with antipsychotics in people with neurodegenerative disease in order to understand if it may be a clinically useful marker.…”

Associations between Trace Elements and Cognitive Decline: An Exploratory 5-Year Follow-Up Study of an Elderly Cohort

“…Furthermore, Se has a very narrow range of safe exposure [95], and both its deficiency and excess are associated with important adverse health effects [96]. In the human body, Se plays an essential antioxidant role [97] and is very important for the maintenance of the homeostasis of the central nervous system [98]. Its beneficial effects are mediated by selenium-containing proteins (the selenoproteins) such as glutathione peroxidases (GPx), the plasma Se-transport protein (SePP), and thioredoxin reductases (TrxR) [99].…”

“…Reduced levels of Se are believed to lead to neurons destruction and increased risk of cognitive decline/dementia [108,109]. Studies show that, compared to healthy elder adults, AD patients exhibited reduced levels of Se in plasma, erythrocyte, blood, cerebrospinal fluid (CSF), and nails [97,[110][111][112]. Specifically, the levels of this TE seem to be decreased in the temporal, hippocampal, and cortex regions of AD patients [113].…”