Affiliations: Center for Cellular Neurobiology and Neurodegeneration Research, Department of Biological Sciences, University of Massachusetts Lowell, Lowell, MA 01854, USA | Center for Cellular Neurobiology and Neurodegeneration Research, University of Massachusetts Lowell, Lowell, MA 01854, USA
Correspondence:
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Corresponding author: T.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: [email protected].
Abstract: One hallmark of AD is the deposition of neurofibrillary tangles which are comprised of phosphorylated isoforms of the microtubule-associated protein tau. We demonstrate herein that dietary deprivation of folate and vitamin E, coupled with iron as a pro-oxidant, fosters an increase in nonphospho- and-phospho-tau within brain tissue of mice homozygously lacking apolipoprotein E as assayed by monoclonal antibodies Tau-1 and PHF-1, respectively. Tau immunoreactivity in mice homozygously expressing murine apolipoprotein E was not affected. Supplementation of this challenge diet with s-adenosylmethinone, known to be depleted following folate deprivation and further known to restore a portion of the oxidative buffering capactity of these mice when maintained under this challenge diet, alleviates the increase in nonphospho-tau but does not attenuate the increase in phospho-tau. These findings suggest that the combined deleterious impact of dietary- and genetically-induced oxidative stress fostered a specific increase in phospho-tau. While some studies consider that increased levels of phospho-tau represents a hallmark of neuropathology, the findings of the present study also remain consistent with the alternative viewpoint that accumulation of phospho-tau instead represents an index of antioxidant compensation.
Keywords: Alzheimer disease, apolipoprotein E, folate, tau phosphorylation, vitamin E
