Atherosclerotic processes are drawing the attention of some Alzheimer's researchers who point to a number of links between atherosclerotic disease and Alzheimer's disease. It is only natural then, that vitamin E, a hot topic in the study of cardiovascular disease, should garner some attention in the Alzheimer's community.

Research into arterial plaque formation suggests that an inflammatory process is involved. A study by Ishwarlal Jialal and Sridevi Devaraj, which appeared in the April 8 Arteriosclerosis, Thrombosis, and Vascular Biology, combines two lines of thought: that some part of this inflammatory process is promoted by the proinflammatory cytokine interleukin-1-β (IL-1-β) and that alpha-tocopherol (vitamin E; AT) can help prevent the formation of arterial plaques, in part by acting on the inflammatory process.

The authors had previously shown that AT has a number of molecular effects in vivo, among them a decrease in IL-1-β release. The present in vitro study, in white blood cells, sought to identify the mechanism of this inhibition. A number of candidate processes were considered, and the results suggest that AT does not inhibit IL-1-β release through protein kinase C inhibition or via the cyclooxygenase-prostaglandin E[2] pathway, nor does it act through a classic chain-breaking antioxidant mechanism. Instead, AT appears to decrease IL-1-β release by inhibiting the pathway that produces leukotriene B[4] from 5-lipoxygnase. The authors also found that AT had no effect on IL-1-β mRNA levels, suggesting a posttranscriptional effect.-Hakon Heimer.

Reference:
Devaraj S, Jialal I. Alpha-tocopherol decreases interleukin-1 beta release from activated human monocytes by inhibition of 5-lipoxygenase. Arterioscler Thromb Vasc Biol 1999 Apr;19(4):1125-33. Abstract

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  1. Inflammation, free radicals, and cytokines are involved in a vascular cascade producing the transformation of macrophages into foam cells between the endothelial cell layer and the basement membrane of a blood vessel leading to formation of an atherosclerotic plaque. Similarly, inflammation, free radicals, and cytokines are opined to be involved in beta-amyloid plaque formation, but probably mediated by microglia--a cell type exhibiting capabilities similar to those of monocytes--leading to the deposition of a pathologically produced peptide. Alternatively, beta-amyloid deposited in blood vessels is located differently; it can be either interdigitated with the basement membrane or in the muscle layer.

    Devaraj and Jialal (Arteriosclerosis, Thrombosis, and Vascular Biology, April 8, 1999; vol. 19) have convincingly demonstrated that Vitamin E (alpha-tocopherol) reduces interleukin-1-beta release from monocytes by inhibition of 5-lipoxygenase (5-LO), thereby attenuating a proposed inflammatory first step in atherosclerotic lesion formation. There is emerging data suggesting that critically stenotic coronary atherosclerosis can precipitate the pre-mature incidence of Alzheimer-like neuropathology in the form of beta-amyloid-containing senile plaques. There is also considerable evidence that there is a vascular component (compromise) in Alzheimer's disease. It can easily be suggested that the process inhibited by Vitamin E at the level of the coronary artery may also be effective at the level of the cerebral vasculature in Alzheimer's disease.

    It is of note that we have recently identified and reported vascular inflammation in Alzheimer's disease brain. We would suggest that vascular inflammation and compromise could contribute to the progressive formation of characteristic neuropathology in Alzheimer's disease, and in turn, the eventual clinical manifestations of the disorder. Therefore, targeting 5-LO as a point of therapeutic intervention in Alzheimer's disease at the cerebrovascular level could possibly disrupt senile plaque formation in the underlying brain tissue before it starts.

    As 5-LO is a membrane translocated enzyme and Vitamin E is known to reduce membrane fluidity, it should also be noted that the mechanism of inhibition could be physical rather than chemical. The decrease in membrane fluidity caused by the Vit E may not allow effective 5-LO translocation.

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Paper Citations

  1. . Alpha-tocopherol decreases interleukin-1 beta release from activated human monocytes by inhibition of 5-lipoxygenase. Arterioscler Thromb Vasc Biol. 1999 Apr;19(4):1125-33. PubMed.

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  1. . Alpha-tocopherol decreases interleukin-1 beta release from activated human monocytes by inhibition of 5-lipoxygenase. Arterioscler Thromb Vasc Biol. 1999 Apr;19(4):1125-33. PubMed.

Primary Papers

  1. . Alpha-tocopherol decreases interleukin-1 beta release from activated human monocytes by inhibition of 5-lipoxygenase. Arterioscler Thromb Vasc Biol. 1999 Apr;19(4):1125-33. PubMed.