T.B. Shea1,3,4, F.J. Ekinci1,4, D. Ortiz1, T.O. Wilson5,1, R.J. Nicolosi1,2,4,6

1Center for Cellular Neurobiology and Neurodegeneration Research. 2Center for Health and Disease Research. 3Departments of Biological Sciences. 4Biochemistry University of MassachusettsoLowell Lowell, MA 01854. 5Nutrix Corporation/AST Products, Billerica, MA 01821. 6Department of Health & Clinical Sciences, University of MassachusettsoLowell Lowell, MA 01854. Correspondence to: T.B. Shea, Center for Cellular Neurobiology and Neurodegeneration Research, Department of Biological Sciences, University of MassachusettsoLowell, Lowell, MA 01854. Tel: 978-934-2881. Fax: 978-934-3044. E-mail: Thomas_Shea@uml.edu. 1 Present address: Dept of Health and Clinical Sciences, UMassoLowell

Abstract: Oxidative stress is a pivotal factor in neuronal degeneration including that induced by exposure to amyloid-beta (Abeta). Treatment with antioxidants such as vitamin E can alleviate Abeta neurotoxicity. However, vitamin E was only marginally effective in clinical trials in Alzheimer's disease. Recent studies indicate that treatment with vitamin E (as a-tocopherol), sodium pyruvate and phosphatidyl choline (PC) is more effective than vitamin E alone against neuronal oxidative stress. We demonstrate herein that treatment of cultured murine cortical neurons with these 3 agents is also more effective than vitamin E alone against Abeta neurotoxicity as assayed by generation of reactive oxygen species and increased levels of phospho-isoforms of the microtubule-associated protein tau. These data underscore the potential efficacy of a combinatorial neuroprotective formulation against Abeta neurotoxicity.

Key words: oxidative stress, antioxidants, vitamin E, apolipoprotein E, neurodegeneration, transgenic mice.