Blood selenium concentrations are significantly lower in patients with Alzheimer’s disease compared to healthy controls. This reduction in selenium concentration is directly associated with the observed reduced levels of the important antioxidant selenoprotein, glutathione peroxidase, in Alzheimer’s disease patients.
These are the conclusions of the authors of a 2017 meta-analysis of 12 case-control studies of selenium concentrations in Alzheimer’s disease patients and healthy controls. The 12 case-control studies comprised 594 Alzheimer’s disease patients and 472 healthy controls [Reddy].
Selenium and Alzheimer’s disease meta-analysis
The results of the systematic review and meta-analysis revealed the following associations:
- Significantly decreased selenium levels were seen in the blood circulation of Alzheimer’s disease patients as compared to healthy controls.
- Decreased selenium levels were also seen in the red blood cells and cerebrospinal fluid of Alzheimer’s patients as compared to healthy controls. However, the difference in selenium concentrations did not reach the level of statistical significance.
- Age matching between the Alzheimer’s disease patients and healthy controls showed decreased selenium levels regardless of the age of the patients. This is interesting because advanced age is considered a risk factor for Alzheimer’s disease.
- Controlling for socio-economic, geographical, and environmental differences also showed the decreased selenium levels in Alzheimer’s disease patients compared to the healthy controls.
- A direct association was seen between decreased selenium levels and glutathione peroxidase levels in Alzheimer’s disease patients.
What is glutathione peroxidase, and why is it important?
The glutathione peroxidases (abbreviated GPx) are a family of antioxidant enzymes (selenoproteins) that reduce and thus neutralize potentially harmful radicals like hydrogen peroxide and lipid hydroperoxides. In so doing, the GPx enzymes lessen the extent of oxidative stress damage.
Oxidative stress damage is defined as the damage to cells and tissues caused by an imbalance between the activity of harmful reactive oxygen species and the neutralizing activity of antioxidants in the body. Oxidative stress damage has been identified as one of the first events preceding the manifestation of Alzheimer’s disease [Reddy].
Given its role as a component in the antioxidant GPx enzymes, selenium in adequate concentrations is necessary for the antioxidant defense of cells and tissues.
The meta-analysis showed significant reductions in selenium levels in Alzheimer’s disease patients and significantly associated reduced levels of GPx levels in Alzheimer’s disease patients [Reddy].
The reduced GPx levels can be interpreted as evidence for the important role of the antioxidant role of GPx and as evidence of the role of oxidative stress damage in Alzheimer’s disease.
Summary
- Selenium and the selenium-dependent seleno-enzymes may act as modulators of brain function if there is an adequate supply of selenium [Schweizer].
- Oxidative stress is a pathological mechanism that quite possibly plays a role in neurodegenerative diseases such as Alzheimer’s disease and Parkinson’s disease [Schwetzer].
- The selenium-dependent glutathione peroxidases and thioredoxin reductases are involved in antioxidant defense and in intra-cellular redox regulation and modulation [Schwetzer].
- Depleted selenium levels are associated with diminished antioxidant seleno-enzyme activity [Schweizer].
- Decreased cellular GPx activity increases sensitivity towards neurotoxins and brain damage. Increased GPx activity resulting from increased selenium supply ameliorates the brain and nervous system damage [Schweizer].
- The role of selenium concentrations and GPx activity in the prevention or delay of the onset of neurodegenerative diseases warrants more extensive investigation.
Sources
Reddy, V. S., Bukkeb, S., Duttc, N., Ranad, P. & Pandeye, A. K. (2017).
A systematic review and meta-analysis of the circulatory, erythrocellular
and CSF selenium levels in Alzheimer’s disease. Journal of Trace Elements in Medicine and Biology, 42, 68–75.
Schweizer, u., Brauner, A. U., Kohrle, J. & Nitsch, R. (2004). Selenium and brain function. Brain Res Rev, 45, 3, 164-178.
The information presented in this review article is not intended as medical advice and should not be construed or used as such.