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Stress, depression, and Alzheimer's disease
Lane Simonian
Posted: Tuesday, February 5, 2019 6:35 PM
Joined: 12/12/2011
Posts: 4982

Stress and depression have been long been thought to increase the risk for Alzheimer's disease.  I think the following study has it right in regards to the mechanism behind this link.

Dysregulation of stress systems and nitric oxide signaling underlies neuronal dysfunction in Alzheimer’s disease



Stress differentially modulates hippocampal NO via constitutive and inducible NOS.

Stress-induced NO signalling dysregulation contributes to development of depression.

Glucocorticoids exacerbate progression of AD pathology.

Several key stress-induced mechanisms are shared in depression and AD.


Stress is a multimodal response involving the coordination of numerous body systems in order to maximize the chance of survival. However, long term activation of the stress response results in neuronal oxidative stress via reactive oxygen and nitrogen species generation, contributing to the development of depression. Stress-induced depression shares a high comorbidity with other neurological conditions including Alzheimer’s disease (AD) and dementia, often appearing as one of the earliest observable symptoms in these diseases. Furthermore, stress and/or depression appear to exacerbate cognitive impairment in the context of AD associated with dysfunctional catecholaminergic signaling. Given there are a number of homologous pathways involved in the pathophysiology of depression and AD, this article will highlight the mechanisms by which stress-induced perturbations in oxidative stress, and particularly NO signaling, contribute to neurodegeneration.