Omega-3 fatty acids such as docosahexaenoic acid activate retinoid X receptor pathways inducing ApoE expression and clearance of Beta-Amyloid with improved cognitive performance and inhibition of brain aging.
Steven R.Brenner, Staff physician, St. Louis University Dept. of Neurology and PsychiatrySBren20979@aol.com
St. Louis, MO
Submitted March 16, 2012
I read the article by Tan [1] et al. who discuss omega-3 fatty acid levels and markers of accelerated brain aging. Docosahexaenoic acid (DHA), a long chain polyunsaturated omega-3 fatty acid, activates the retinoid X receptor (RXR) signaling pathway. [2] The RXR agonist, bexarotene, has recently been found to clear beta-amyloid deposits from brains of Alzheimer disease mouse models, by transcriptionally inducing apolipoprotein E (ApoE) through nuclear peroxisome proliferator activated receptors and liver X receptors in coordination with RXR. Activation of RXR stimulated physiological ABeta clearance mechanisms and resulted in rapid reversal of A-Beta induced deficits. [3] Higher levels of the omega-3 fatty acid, DHA, through activation of the RXR signaling pathways, may result in increased ApoE and subsequent clearance of soluble beta-amyloid, resulting in improved cognitive function and inhibition of brain aging.
1. Tan ZS, Harris WS, Beiser AS, et al. Red blood cell omega-3 fatty acid levels and markers of accelerated brain aging. Neurology 2012; 78: 658-664.
2. de Urquiza AM, Liu S, Sjoberg M, et al. Docosahexaenoic acid, a ligand for the retinoid X receptor in mouse brain. Science 2000; 290: 2140-2144.
3. Cramer PE, Cirrito JR, Wesson DW, et al. ApoE-Directed therapeutic rapidly clear B-Amyloid and Reverse Deficits in AD Mouse Models. Science 2012 Feb 9. (Epub ahead of print).
For disclosures, contact editorial office at journal@neurology.org.
I read the article by Tan [1] et al. who discuss omega-3 fatty acid levels and markers of accelerated brain aging. Docosahexaenoic acid (DHA), a long chain polyunsaturated omega-3 fatty acid, activates the retinoid X receptor (RXR) signaling pathway. [2] The RXR agonist, bexarotene, has recently been found to clear beta-amyloid deposits from brains of Alzheimer disease mouse models, by transcriptionally inducing apolipoprotein E (ApoE) through nuclear peroxisome proliferator activated receptors and liver X receptors in coordination with RXR. Activation of RXR stimulated physiological ABeta clearance mechanisms and resulted in rapid reversal of A-Beta induced deficits. [3] Higher levels of the omega-3 fatty acid, DHA, through activation of the RXR signaling pathways, may result in increased ApoE and subsequent clearance of soluble beta-amyloid, resulting in improved cognitive function and inhibition of brain aging.
1. Tan ZS, Harris WS, Beiser AS, et al. Red blood cell omega-3 fatty acid levels and markers of accelerated brain aging. Neurology 2012; 78: 658-664.
2. de Urquiza AM, Liu S, Sjoberg M, et al. Docosahexaenoic acid, a ligand for the retinoid X receptor in mouse brain. Science 2000; 290: 2140-2144.
3. Cramer PE, Cirrito JR, Wesson DW, et al. ApoE-Directed therapeutic rapidly clear B-Amyloid and Reverse Deficits in AD Mouse Models. Science 2012 Feb 9. (Epub ahead of print).
For disclosures, contact editorial office at journal@neurology.org.