Dietary and genetically-induced oxidative stress alter tau phosphorylation: influence of folate and apolipoprotein E...

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.