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Front. Pharmacol. | doi: 10.3389/fphar.2019.00976

Risk factors for Alzheimer's disease: focus on stress

  • 1Sapienza University of Rome, Italy
  • 2Mediterranean Neurological Institute (IRCCS), Italy

In vulnerable individuals, chronic and persistent stress is an established risk factor for disorders that are comorbid with Alzheimer’s disease (AD), such as hypertension, obesity and metabolic syndrome, and psychiatric disorders. There are no disease-modifying drugs in the treatment of AD, and all phase-3 clinical trials with anti-amyloid drugs (e.g., - or -secretase inhibitors and monoclonal antibodies) did not meet the primary endpoints. There are many reasons for the lack of efficacy of anti-amyloid drugs in AD, the most likely being a late start of treatment, considering that pathophysiological mechanisms underlying synaptic dysfunction and neuronal death begin several decades prior to the clinical onset of AD. The identification of risk factors is therefore an essential step for an early treatment of AD with candidate disease-modifying drugs. Preclinical studies suggest that stress, and resulting activation of the hypothalamic-pituitary-adrenal axis, can induce biochemical abnormalities reminiscent to those found in autoptic brain samples from individuals affected by AD (e.g., increases amyloid precursor protein and tau hyperphosphorylation). In this review, we will critically analyze the current knowledge supporting stress as a potential risk factor for AD.

Keywords: stress, glucococorticoids, Alzheheimer's disease, risk factor, animal model

Received: 24 May 2019; Accepted: 31 Jul 2019.

Copyright: © 2019 Scaccianoce, Caruso, Nicoletti and Gaetano. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

* Correspondence: Dr. Sergio Scaccianoce, Sapienza University of Rome, Rome, Italy,