title: 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.
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.
authors.affiliation: Center for Cellular Neurobiology and Neurodegeneration Research, Department of Biological Sciences, University of Massachusetts Lowell, Lowell, Massachusetts 01854, USA.
authors.forename: Amy
authors.initials: A
authors.lastname: Chan
authors.forename: Thomas B
authors.initials: TB
authors.lastname: Shea
mesh_terms: D000544:Alzheimer Disease / Q000188:drug therapy / Q000378:metabolism* / Q000503:physiopathology; D053829:Amyloid Precursor Protein Secretases / Q000378:metabolism*; D016229:Amyloid beta-Peptides / Q000096:biosynthesis*; D000818:Animals; D001057:Apolipoproteins E / Q000172:deficiency*; D001921:Brain / Q000187:drug effects / Q000378:metabolism* / Q000503:physiopathology; D019587:Dietary Supplements; D005494:Folic Acid Deficiency / Q000378:metabolism* / Q000503:physiopathology; D005526:Food, Formulated; D019266:Iron, Dietary / Q000009:adverse effects; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D018384:Oxidative Stress / Q000187:drug effects / Q000502:physiology; D053763:Presenilins / Q000378:metabolism*; D012436:S-Adenosylmethionine / Q000494:pharmacology* / Q000627:therapeutic use; D015854:Up-Regulation / Q000187:drug effects / Q000502:physiology; D014811:Vitamin E Deficiency / Q000378:metabolism / Q000503:physiopathology
chemical_list: D016229:Amyloid beta-Peptides; D001057:Apolipoproteins E; D019266:Iron, Dietary; D053763:Presenilins; D012436:S-Adenosylmethionine; D053829:Amyloid Precursor Protein Secretases