Supplementation with apple juice attenuates presenilin-1 overexpression during dietary and genetically-induced oxidative stress

J Alzheimers Dis. 2006 Dec;10(4):353-8. doi: 10.3233/jad-2006-10401.


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.

MeSH terms

  • Acetylcholine / metabolism
  • Age Factors
  • Alzheimer Disease / genetics*
  • Alzheimer Disease / physiopathology
  • Animals
  • Antioxidants / pharmacology*
  • Apolipoproteins E / deficiency
  • Apolipoproteins E / physiology
  • Beverages*
  • Brain / drug effects
  • Brain / metabolism
  • DNA Methylation / drug effects
  • Disease Models, Animal*
  • Folic Acid Deficiency / genetics
  • Folic Acid Deficiency / physiopathology
  • Gene Expression Regulation / drug effects*
  • Gene Expression Regulation / physiology
  • Humans
  • Malus*
  • Mice
  • Mutation / drug effects
  • Mutation / genetics
  • Neuroprotective Agents / pharmacology*
  • Oxidative Stress / drug effects*
  • Oxidative Stress / genetics*
  • Oxidative Stress / physiology
  • Presenilin-1 / genetics*
  • Reactive Oxygen Species / metabolism
  • S-Adenosylmethionine / pharmacology
  • Vitamin E Deficiency / genetics
  • Vitamin E Deficiency / physiopathology


  • Antioxidants
  • Apolipoproteins E
  • Neuroprotective Agents
  • PSEN1 protein, human
  • Presenilin-1
  • Reactive Oxygen Species
  • S-Adenosylmethionine
  • Acetylcholine