Dietary Deficiency in Folate and Vitamin E Under Conditions of Oxidative Stress Increases Phospho-Tau Levels: Potentiation by ApoE4 and Alleviation by S-Adenosylmethionine
Affiliations: Center for Cellular Neurobiology and Neurodegeneration Research, Department of Biological Sciences, Department of Clinical and Health Sciences, University of Massachusetts Lowell, Lowell, MA, USA
Correspondence:
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Corresponding author: Thomas B. Shea, PhD, Center for Cellular Neurobiology and Neurodegeneration Research, Department of Biological Sciences, University of Massachusetts Lowell, One University Avenue, Lowell, MA 01854, USA. Tel.: +1 978 934 2881, Fax: +1 978 934 3044; E-mail: Thomas_Shea@uml.edu.
Note: [1] Present address: Alnylam Pharmaceuticals, Cambridge, MA 02142, USA.
Abstract: Prior studies link dietary deficiency and genetic risk factors for Alzheimer's disease (AD). In the present report, mice expressing human apolipoprotein E4 (associated with increased risk of AD) and apolipoprotein E3 were subjected to a diet lacking folate and vitamin E, and containing iron as a pro-oxidant. Consistent with prior studies, E4 mice displayed more phospho-tau than E3 mice prior to dietary challenge. The deficient diet increased phospho-tau in E4 but not E3 mice, which was prevented by S-adenosyl methionine supplementation. Since neurofibrillary tangles are comprised of phospho-tau, investigation of the impact of dietary deficiency and S-adenosyl methionine supplementation on neurofibrillary tangle formation are warranted.
Keywords: Apolipoprotein E, folate, S-adenosyl methionine, tau, vitamin E
