Background: Translational research needs valid animal models of disease to discover new pathogenetic aspects and treatments. In Alzheimer's disease (AD), transgenic models are of great value for AD research and drug testing. Objective: It was the aim of this study to analyze the power of dietary polyphenols against neurodegeneration by investigating the effects of oleuropein aglycone (OLE), the main phenol in the extra virgin olive oil (EVOO), a key component of the Mediterranean diet (MD), in a mouse model of amyloid-β deposition. Methods: TgCRND8 mice (3.5 months old), expressing the mutant KM670/671NL+V717F h-βAPP695 transgene, and wild-type (wt) mice were used to study in vivo the effects of an 8-week dietary supplementation with OLE (50 mg/kg of diet) [Grossi et al: PLoS One 2013;8:e71702], following the European Communities Council Directive 86/609 (DL 116/92) and National Guidelines (permit number: 283/2012-B). Results: OLE administration ameliorates memory dysfunction, raises a significant autophagic response in the cortex and promotes the proliferation of newborn cells in the subgranular zone of the dentate gyrus of the hippocampus. Conclusions: Our findings support the beneficial effects of EVOO and highlight the possibility that continuous intake of high doses of OLE, both as a nutraceutical or as a food integrator, may prevent/delay the appearance of AD and reduce the severity of its symptoms.

Keywords:
TgCRND8 mice, Oleuropein aglycone, Autophagy, Adult hippocampal neurogenesis
1.
Casamenti F, Di Patre PL, Bartolini L, et al: Unilateral and bilateral nucleus basalis lesions: differences in neurochemical and behavioral recovery. Neuroscience 1988;24:209-215.
2.
Giovannelli L, Casamenti F, Scali C, et al: Differential effects of amyloid peptides beta-(1-40) and beta-(25-35) injections into the rat nucleus basalis. Neuroscience 1995;66:781-792.
3.
LaFerla FM, Green KN: Animal models of Alzheimer disease. Cold Spring Harb Perspect Med 2012;2:a006320.
4.
Rockenstein E, Crews L, Masliah E, et al: Transgenic animal models of neurodegenerative diseases and their application to treatment development. Adv Drug Deliv Rev 2007;59:1093-1102.
5.
Paquet D, Schmid B, Haass C, et al: Transgenic Zebrafish as a novel animal model to study tauopathies and other neurodegenerative disorders in vivo. Neurodegener Dis 2010;7:99-102.
6.
Cohen RM, Rezai-Zadeh K, Weitz TM, et al: A transgenic Alzheimer rat with plaques, tau pathology, behavioral impairment, oligomeric Aβ, and frank neuronal loss. J Neurosci 2013;33:6245-6256.
7.
Zhang L, Chang RC, Chu LW, et al: Current neuroimaging techniques in Alzheimer's disease and applications in animal models. Am J Nucl Med Mol Imaging 2012;2:386-404.
8.
Rubinsztein DC, Marino G, Kroemer G, et al: Autophagy and aging. Cell 2011;146:682-695.
9.
Mizushima N, Komatsu M: Autophagy: renovation of cells and tissues. Cell 2011;147:728-741.
10.
Ho L, Chen LH, Wang J, et al: Heterogeneity in red wine polyphenolic contents differentially influences Alzheimer's Disease-type neuropathology and cognitive deterioration. J Alzheimers Dis 2009;16:59-72.
11.
Feart C, Samieri C, Rondeau V, et al: Adherence to a Mediterranean diet, cognitive decline, and risk of dementia. JAMA 2009;302:638-648.
12.
Pitozzi V, Jacomelli M, Zaid M, et al: Effects of dietary extra-virgin olive oil on behaviour and brain biochemical parameters in ageing rats. Br J Nutr 2010;103:1674-1683.
13.
Karuppagounder SS, Pinto JT, Xu H, et al: Dietary supplementation with resveratrol reduces plaque pathology in a transgenic model of Alzheimer's disease. Neurochem Int 2009;54:111-118.
14.
Grossi C, Rigacci S, Ambrosini S, et al: The polyphenol oleuropein aglycone protects TgCRND8 mice against Aβ plaque pathology. PLoS One 2013;8:e71702.
15.
Bellucci A, Rosi MC, Grossi C, et al: Abnormal processing of tau in the brain of aged TgCRND8 mice. Neurobiol Dis 2007;27:328-338.
16.
Fiorentini A, Rosi MC, Grossi C, et al: Lithium improves hippocampal neurogenesis, neuropathology and cognitive functions in APP mutant mice. PLoS One 2010;5:e14382.
© 2013 S. Karger AG, Basel
2013
Copyright / Drug Dosage / Disclaimer
Copyright: All rights reserved. No part of this publication may be translated into other languages, reproduced or utilized in any form or by any means, electronic or mechanical, including photocopying, recording, microcopying, or by any information storage and retrieval system, without permission in writing from the publisher.
Drug Dosage: The authors and the publisher have exerted every effort to ensure that drug selection and dosage set forth in this text are in accord with current recommendations and practice at the time of publication. However, in view of ongoing research, changes in government regulations, and the constant flow of information relating to drug therapy and drug reactions, the reader is urged to check the package insert for each drug for any changes in indications and dosage and for added warnings and precautions. This is particularly important when the recommended agent is a new and/or infrequently employed drug.
Disclaimer: The statements, opinions and data contained in this publication are solely those of the individual authors and contributors and not of the publishers and the editor(s). The appearance of advertisements or/and product references in the publication is not a warranty, endorsement, or approval of the products or services advertised or of their effectiveness, quality or safety. The publisher and the editor(s) disclaim responsibility for any injury to persons or property resulting from any ideas, methods, instructions or products referred to in the content or advertisements.
You do not currently have access to this content.