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oxidant stress induced by dietary iron
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Journal of Neurochemistry
Volume 102 Issue 3 Page 753-760, August 2007

Abstract
Folate deprivation increases presenilin expression, gamma-secretase
activity, and Abeta levels in murine brain: potentiation by ApoE
deficiency and alleviation by dietary S-adenosyl methionine
Amy Chan and Thomas B. Shea
Center for Cellular Neurobiology and Neurodegeneration Research,
Department of Biological Sciences, University of Massachusetts Lowell,
Lowell, Massachusetts, USA
Abstract

Folate deficiency has been associated with age-related
neurodegeneration. One direct consequence of folate deficiency is a
decline in the major methyl donor, S-adenosyl methionine (SAM). We
demonstrate herein that dietary deficiency in folate and vitamin E,
coupled pro-oxidant stress induced by dietary iron, increased
presenilin-1 expression, gamma-secretase activity, and Abeta levels in
normal adult mice. These increases were potentiated by apolipoprotein
E deficiency as shown by treatment of transgenic mice homozygously
lacking murine apolipoprotein E. Dietary supplementation with SAM in
the absence of folate attenuated or alleviated these deleterious
consequences. These findings link nutritional and genetic risk factors
for age-related neurodegeneration and underscore that dietary
supplementation with SAM may be useful to augment therapeutic
approaches.

Address correspondence and reprint requests to Thomas B. Shea, Center
for Cellular Neurobiology and Neurodegeneration Research, Department
of Biological Sciences, University of Massachusetts Lowell, Lowell, MA
01854, USA.
E-mail: Thomas_Shea@uml.edu

glyceraldehyde phosphate dehydrogenase; MTHFR, 5,10-
methylenetetrahydrofolate reductase; PS-1, presenilin-1.

To cite this article: Amy Chan, Thomas B. Shea (2007)
Folate deprivation increases presenilin expression, gamma-secretase
activity, and Abeta levels in murine brain: potentiation by ApoE
deficiency and alleviation by dietary S-adenosyl methionine
Journal of Neurochemistry 102 (3), 753-760.
doi:10.1111/j.1471-4159.2007.04589.x