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Reviews in the Neurosciences

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Volume 25, Issue 6 (Dec 2014)


Chronic stress as a risk factor for Alzheimer’s disease

Alberto Machado
  • Facultad de Farmacia, Departamento de Bioquímica y Biología Molecular, Universidad de Sevilla, c/o Profesor García González, 2, E-41012 Sevilla, Spain
  • Instituto de Biomedicina de Sevilla (IBiS)-Hospital Universitario Virgen del Rocío/CSIC/Universidad de Sevilla, E-41013 Sevilla, Spain
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/ Antonio J. Herrera
  • Facultad de Farmacia, Departamento de Bioquímica y Biología Molecular, Universidad de Sevilla, c/o Profesor García González, 2, E-41012 Sevilla, Spain
  • Instituto de Biomedicina de Sevilla (IBiS)-Hospital Universitario Virgen del Rocío/CSIC/Universidad de Sevilla, E-41013 Sevilla, Spain
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/ Rocío M. de Pablos
  • Corresponding author
  • Facultad de Farmacia, Departamento de Bioquímica y Biología Molecular, Universidad de Sevilla, c/o Profesor García González, 2, E-41012 Sevilla, Spain
  • Instituto de Biomedicina de Sevilla (IBiS)-Hospital Universitario Virgen del Rocío/CSIC/Universidad de Sevilla, E-41013 Sevilla, Spain
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/ Ana María Espinosa-Oliva
  • Facultad de Farmacia, Departamento de Bioquímica y Biología Molecular, Universidad de Sevilla, c/o Profesor García González, 2, E-41012 Sevilla, Spain
  • Instituto de Biomedicina de Sevilla (IBiS)-Hospital Universitario Virgen del Rocío/CSIC/Universidad de Sevilla, E-41013 Sevilla, Spain
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/ Manuel Sarmiento
  • Facultad de Farmacia, Departamento de Bioquímica y Biología Molecular, Universidad de Sevilla, c/o Profesor García González, 2, E-41012 Sevilla, Spain
  • Instituto de Biomedicina de Sevilla (IBiS)-Hospital Universitario Virgen del Rocío/CSIC/Universidad de Sevilla, E-41013 Sevilla, Spain
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/ Antonio Ayala
  • Facultad de Farmacia, Departamento de Bioquímica y Biología Molecular, Universidad de Sevilla, c/o Profesor García González, 2, E-41012 Sevilla, Spain
  • Instituto de Biomedicina de Sevilla (IBiS)-Hospital Universitario Virgen del Rocío/CSIC/Universidad de Sevilla, E-41013 Sevilla, Spain
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/ José Luis Venero
  • Facultad de Farmacia, Departamento de Bioquímica y Biología Molecular, Universidad de Sevilla, c/o Profesor García González, 2, E-41012 Sevilla, Spain
  • Instituto de Biomedicina de Sevilla (IBiS)-Hospital Universitario Virgen del Rocío/CSIC/Universidad de Sevilla, E-41013 Sevilla, Spain
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/ Martiniano Santiago
  • Facultad de Farmacia, Departamento de Bioquímica y Biología Molecular, Universidad de Sevilla, c/o Profesor García González, 2, E-41012 Sevilla, Spain
  • Instituto de Biomedicina de Sevilla (IBiS)-Hospital Universitario Virgen del Rocío/CSIC/Universidad de Sevilla, E-41013 Sevilla, Spain
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/ Ruth F. Villarán
  • Facultad de Farmacia, Departamento de Bioquímica y Biología Molecular, Universidad de Sevilla, c/o Profesor García González, 2, E-41012 Sevilla, Spain
  • Instituto de Biomedicina de Sevilla (IBiS)-Hospital Universitario Virgen del Rocío/CSIC/Universidad de Sevilla, E-41013 Sevilla, Spain
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/ María José Delgado-Cortés
  • Facultad de Farmacia, Departamento de Bioquímica y Biología Molecular, Universidad de Sevilla, c/o Profesor García González, 2, E-41012 Sevilla, Spain
  • Instituto de Biomedicina de Sevilla (IBiS)-Hospital Universitario Virgen del Rocío/CSIC/Universidad de Sevilla, E-41013 Sevilla, Spain
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/ Sandro Argüelles
  • Facultad de Farmacia, Departamento de Bioquímica y Biología Molecular, Universidad de Sevilla, c/o Profesor García González, 2, E-41012 Sevilla, Spain
  • Instituto de Biomedicina de Sevilla (IBiS)-Hospital Universitario Virgen del Rocío/CSIC/Universidad de Sevilla, E-41013 Sevilla, Spain
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/ Josefina Cano
  • Facultad de Farmacia, Departamento de Bioquímica y Biología Molecular, Universidad de Sevilla, c/o Profesor García González, 2, E-41012 Sevilla, Spain
  • Instituto de Biomedicina de Sevilla (IBiS)-Hospital Universitario Virgen del Rocío/CSIC/Universidad de Sevilla, E-41013 Sevilla, Spain
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Published Online: 2014-08-29 | DOI: https://doi.org/10.1515/revneuro-2014-0035


This review aims to point out that chronic stress is able to accelerate the appearance of Alzheimer’s disease (AD), proposing the former as a risk factor for the latter. Firstly, in the introduction we describe some human epidemiological studies pointing out the possibility that chronic stress could increase the incidence, or the rate of appearance of AD. Afterwards, we try to justify these epidemiological results with some experimental data. We have reviewed the experiments studying the effect of various stressors on different features in AD animal models. Moreover, we also point out the data obtained on the effect of chronic stress on some processes that are known to be involved in AD, such as inflammation and glucose metabolism. Later, we relate some of the processes known to be involved in aging and AD, such as accumulation of β-amyloid, TAU hyperphosphorylation, oxidative stress and impairement of mitochondrial function, emphasizing how they are affected by chronic stress/glucocorticoids and comparing with the description made for these processes in AD. All these data support the idea that chronic stress could be considered a risk factor for AD.

Keywords: aging; amyloid-β; glucocorticoids; neuroinflammation


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About the article

Corresponding author: Rocío M. de Pablos, Facultad de Farmacia, Departamento de Bioquímica y Biología Molecular, Universidad de Sevilla, c/o Profesor García González, 2, E-41012 Sevilla, Spain, e-mail:

aPresent address: Gray Institute for Radiation Oncology and Biology, Department of Oncology, University of Oxford, Oxford OX3 7LJ, UK

bPresent address: National Institutes of Health, National Institute on Aging, Biomedical Research Center, Laboratory of Neurosciences, 251 Bayview Boulevard, Baltimore, MD 21224, USA


Received: 2014-05-16

Accepted: 2014-07-11

Published Online: 2014-08-29

Published in Print: 2014-12-01

Citation Information: Reviews in the Neurosciences, ISSN (Online) 2191-0200, ISSN (Print) 0334-1763, DOI: https://doi.org/10.1515/revneuro-2014-0035.

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