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Licensed Unlicensed Requires Authentication Published by De Gruyter August 29, 2014

Chronic stress as a risk factor for Alzheimer’s disease

  • Alberto Machado , Antonio J. Herrera , Rocío M. de Pablos EMAIL logo , Ana María Espinosa-Oliva , Manuel Sarmiento , Antonio Ayala , José Luis Venero , Martiniano Santiago , Ruth F. Villarán , María José Delgado-Cortés , Sandro Argüelles and Josefina Cano


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.

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


This work was supported by grant SAF-2012-39029 from the Spanish Ministry of Economy and Competitiveness and P10-CTS-6494 (Proyecto de Excelencia of Junta de Andalucia).

Conflicts of interest statement: The authors declare that they have no conflicts of interest.


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Received: 2014-5-16
Accepted: 2014-7-11
Published Online: 2014-8-29
Published in Print: 2014-12-1

©2014 by De Gruyter

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