Selenium Modulation in Alzheimer's Disease Models

Selenium, an essential trace element, has emerged as a promising modulator of pathological processes in experimental models of Alzheimer’s disease (AD). Its incorporation into selenoproteins underpins potent antioxidant defence systems that counteract oxidative stress, a key driver of neuronal damage. Selenium compounds influence amyloid-β production and aggregation, mitigate tau hyperphosphorylation, and restore synaptic integrity. Diverse forms of selenium, including inorganic selenate and organic selenomethionine, differ in bioavailability, biodistribution and target pathways. In transgenic mouse models, chronic dietary supplementation of sodium selenate reverses cognitive deficits and attenuates neuropsychiatric symptoms by reducing aggregated tau without altering amyloid plaques. Parallel studies reveal that long-term selenate administration reshapes the brain ionome, rebalancing metal homeostasis and enhancing activities of thioredoxin reductase and glutathione peroxidase. Alternative selenium compounds demonstrate differential regulation of selenoenzymes to modulate glycogen synthase kinase-3β activity, mitochondrial function and synaptic protein expression. Collectively, these findings position selenium modulation as a multifaceted approach to intervene in AD-like pathology, with global significance for nutritional and therapeutic strategies.

Research from Nature Portfolio

Foundational work in transgenic models has shown that prolonged sodium selenate supplementation at advanced disease stages reverses hippocampal-dependent learning and memory impairments and alleviates anxiety-like and depressive-like behaviours. These benefits correlate with a marked reduction in aggregated tau and reactive astrocytes, indicating a tau-targeted mechanism independent of amyloid-β clearance. Complementary ionomic analyses reveal that high-dose selenate restores dysregulated metal profiles in the AD brain, notably normalising iron levels across multiple time points. This mineral rebalancing is coupled with increased activity of key selenoenzymes, suggesting that selenium enrichment orchestrates a broader crosstalk among trace elements to reinforce antioxidative defences and proteostatic pathways.

Selenium Modulation in Alzheimer's Disease Models publication trend

The graph below shows the total number of articles in selenium modulation in alzheimer's disease models across all publications each year (not limited to Nature Index journals).

Technical terms

Selenoenzyme: A protein incorporating selenium, typically as selenocysteine, that catalyses antioxidative and redox-regulating reactions.

Amyloid-β: Peptides derived from amyloid precursor protein that aggregate to form extracellular plaques in Alzheimer’s disease.

Tau hyperphosphorylation: Excessive addition of phosphate groups to tau protein, leading to neurofibrillary tangles and microtubule destabilisation.

Brain ionome: The complete profile of elemental composition and interactions within the brain, including trace metals and minerals.

Oxidative stress: A state of imbalance between reactive oxygen species production and antioxidant defences, causing cellular damage.

References

1. Different Effects and Mechanisms of Selenium Compounds in Improving Pathology in Alzheimer’s Disease. Antioxidants (2023).
2. Effects of Selenium Supplementation in Patients with Mild Cognitive Impairment or Alzheimer’s Disease: A Systematic Review and Meta-Analysis. Nutrients (2022).
3. Reversal of memory and neuropsychiatric symptoms and reduced tau pathology by selenium in 3xTg-AD mice. Scientific Reports (2018).
4. Sodium selenate regulates the brain ionome in a transgenic mouse model of Alzheimer’s disease. Scientific Reports (2016).
5. Selenomethionine Improves Mitochondrial Function by Upregulating Mitochondrial Selenoprotein in a Model of Alzheimer’s Disease. Frontiers in Aging Neuroscience (2021).