Dietary and genetically-induced oxidative stress alter tau phosphorylation: influence of folate and apolipoprotein E deficiency.
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.
Chan
Amy
A
Center for Cellular Neurobiology and Neurodegeneration Research, Department of Biological Sciences, University of Massachusetts Lowell, One University Avenue, Lowell, MA 01854, USA.
Shea
Thomas B
TB
D000544:Alzheimer Disease / Q000235:genetics* / Q000378:metabolism* / Q000473:pathology; D000818:Animals; D001057:Apolipoproteins E / Q000097:blood / Q000172:deficiency*; D001921:Brain / Q000378:metabolism* / Q000473:pathology; D004032:Diet; D005494:Folic Acid Deficiency / Q000378:metabolism*; D005625:Frontal Lobe / Q000378:metabolism / Q000473:pathology; D007031:Hypothalamus / Q000378:metabolism / Q000473:pathology; D051379:Mice; D008810:Mice, Inbred C57BL; D016874:Neurofibrillary Tangles / Q000378:metabolism; D018384:Oxidative Stress / Q000235:genetics*; D010766:Phosphorylation; D012436:S-Adenosylmethionine / Q000008:administration & dosage; D014811:Vitamin E Deficiency / Q000378:metabolism*; D016875:tau Proteins / Q000378:metabolism*
D001057:Apolipoproteins E; D016875:tau Proteins; D012436:S-Adenosylmethionine