title: Supplementation with apple juice attenuates presenilin-1 overexpression during dietary and genetically-induced oxidative stress.
abstract: Gain-of-function mutations in the presenilin-1 (PS-1) promote Alzheimer's disease (AD) by increasing reactive oxygen species, at least part of which is derived by an accompanying increase in generation of amyloid-beta (Abeta). Additional studies indicate that impaired Apolipoprotein E function, which also increases oxidative stress and is also associated with AD, potentiates the deleterious activity of PS-1. Folate deficiency is also associated with AD and potentiates the impact of both ApoE deficiency and beta exposure. More recently, folate deficiency has been shown to increase PS-1 expression. Since dietary supplementation with apple juice provides neuroprotection against ApoE deficiency, Abeta exposure and folate deficiency, we examined the impact of apple juice on PS-1 overexpression. Herein, we demonstrate that dietary deficiency in folate and vitamin E increased PS-1 expression in juvenile and adult normal C57B1/6J and ApoE-/- mice and in aged normal mice. Supplementation with apple juice concentrate (AJC) attenuated or prevent these increases. Prior studies demonstrate that impaired DNA methylation resulting from a deficiency in S-adenosylmethionine (SAM, which is rapidly depleted following folate deprivation) leads to PS-1 overexpression, and that direct supplementation with SAM attenuates PS-1 overexpression. We determined that AJC contained levels of SAM comparable to those capable of suppressing PS-1 overexpression, suggesting that the SAM content of AJC represents a potential mechanism for preventing PS-1 overexpression, and further highlighting the possibility that AJC provides neuroprotection by mechanisms in addition to its antioxidant potential.
authors.affiliation: Department of Biological Sciences, Center for Cellular Neurobiology and Neurodegeneration Research, University of Massachusetts, Lowell, MA 01854, USA.
authors.forename: Amy
authors.initials: A
authors.lastname: Chan
authors.forename: Thomas B
authors.initials: TB
authors.lastname: Shea
mesh_terms: D000109:Acetylcholine / Q000378:metabolism; D000367:Age Factors; D000544:Alzheimer Disease / Q000235:genetics* / Q000503:physiopathology; D000818:Animals; D000975:Antioxidants / Q000494:pharmacology*; D001057:Apolipoproteins E / Q000172:deficiency / Q000502:physiology; D001628:Beverages; D001921:Brain / Q000187:drug effects / Q000378:metabolism; D019175:DNA Methylation / Q000187:drug effects; D004195:Disease Models, Animal; D005494:Folic Acid Deficiency / Q000235:genetics / Q000503:physiopathology; D005786:Gene Expression Regulation / Q000187:drug effects* / Q000502:physiology; D006801:Humans; D027845:Malus; D051379:Mice; D009154:Mutation / Q000187:drug effects / Q000235:genetics; D018696:Neuroprotective Agents / Q000494:pharmacology*; D018384:Oxidative Stress / Q000187:drug effects* / Q000235:genetics* / Q000502:physiology; D053764:Presenilin-1 / Q000235:genetics*; D017382:Reactive Oxygen Species / Q000378:metabolism; D012436:S-Adenosylmethionine / Q000494:pharmacology; D014811:Vitamin E Deficiency / Q000235:genetics / Q000503:physiopathology
chemical_list: D000975:Antioxidants; D001057:Apolipoproteins E; D018696:Neuroprotective Agents; C508853:PSEN1 protein, human; D053764:Presenilin-1; D017382:Reactive Oxygen Species; D012436:S-Adenosylmethionine; D000109:Acetylcholine