Caloric restriction attenuates Aβ-deposition in Alzheimer transgenic models

Received 13 May 2004; received in revised form 13 August 2004; accepted 20 September 2004.

Abstract

Dietary influences on Alzheimer disease (AD) are gaining recognition. Because many aging processes are attenuated in laboratory mammals by caloric restriction (CR), we examined the effects of short-term CR in two AD-transgenic mice, APPswe/ind (J20) and APPswe+PS1M146L (APP+PS1). CR substantially decreased the accumulation of Aβ-plaques in both lines: by 40% in APPswe/ind (CR, 6 weeks), and by 55% in APP+PS1 (CR, 14 weeks). CR also decreased astrocytic activation (GFAP immunoreactivity). These influences of CR on AD-transgenic mice are consistent with epidemiological reports that show that high caloric diets associate with the risk of AD, and suggest that dietary interventions in adult life might slow disease progression.

Keywords: Caloric restriction, AD transgenics, Amyloid deposition, Astrocyte activation

a Andrus Gerontology Center and Department of Biological Sciences, University of Southern California, Los Angeles, CA 90089-0191, USA

b Alzheimer's Research Laboratory, Department of Pharmacology, University of South Florida, Tampa, FL 33162, USA

c Alzheimer's Research Laboratory, Department of Pediatrics, University of South Florida, Tampa, FL 33162, USA

Corresponding author. Tel.: +1 213 740 4083; fax: +1 213 740 0853.

1 Present address: Department of Gene Expression and Drug Discovery, City of Hope National Cancer Center, Duarte, CA 91010, USA.

2 T.E.M. and C.E.F. contributed equally to this work.

PII: S0197-4580(04)00307-0

doi:10.1016/j.neurobiolaging.2004.09.014

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