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Article type: Research Article
Authors: Chan, Amy | Shea, Thomas B.; *
Affiliations: Department of Biological Sciences, Center for Cellular Neurobiology and Neurodegeneration Research, Department of Biological Sciences, University of Massachusetts, Lowell, MA 01854, USA
Correspondence: [*] Corresponding author. Tel.: +1 978 934 2881; Fax: +1 978 934 3044; E-mail: [email protected].
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-β (Aβ). 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 β exposure. More recently, folate deficiency has been shown to increase PS-1 expression. Since dietary supplementation with apple juice provides neuroprotection against ApoE deficiency, Aβ 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.
Keywords: Alzheimer disease, antioxidants, apolipoprotein E, oxidative stress, presenilin, s-adenosylmethionine
DOI: 10.3233/JAD-2006-10401
Journal: Journal of Alzheimer's Disease, vol. 10, no. 4, pp. 353-358, 2006
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