Chronic stress may contribute to Alzheimer’s disease development

Chronic stress may contribute to Alzheimer’s disease development
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A new review has provided insights on the link between chronic stress and Alzheimer’s disease.

Chronic psychosocial stress, which involves a pathway called the hypothalamic-pituitary-adrenal axis (HPA axis), could be a contributor to the development of Alzheimer’s disease according to a new review, published in Biological Reviews.

The review has described how environmental and genetic factors can impact individuals’ HPA axis, and ultimately their risk of Alzheimer’s disease.

Genetic factors

The review proposes a mechanism by which genetic factors that influence the HPA axis may also affect inflammation, a key driver of neurodegeneration.

Senior author David Groth, PhD, of Curtin University, in Australia, said: “What we know is that chronic stress does affect many biological pathways within our body. There is an intimate interplay between exposure to chronic stress and pathways influencing the body’s reaction to such stress.

“Genetic variations within these pathways can influence the way the brain’s immune system behaves leading to a dysfunctional response. In the brain, this leads to a chronic disruption of normal brain processes, increasing the risk of subsequent neurodegeneration and ultimately dementia.”

The review states: “Chronic psychosocial stress is increasingly being recognised as a risk factor for sporadic Alzheimer’s disease (AD). The hypothalamic–pituitary–adrenal axis (HPA axis) is the major stress response pathway in the body and tightly regulates the production of cortisol, a glucocorticoid hormone. Dysregulation of the HPA axis and increased levels of cortisol are commonly found in AD patients and make a major contribution to the disease process.

“The underlying mechanisms remain poorly understood. In addition, within the general population there are interindividual differences in sensitivities to glucocorticoid and stress responses, which are thought to be due to a combination of genetic and environmental factors. These differences could ultimately impact an individuals’ risk of AD.”

It continues: “We hypothesize that these factors can mediate glucocorticoid priming of the immune cells of the brain, microglia, to become pro-inflammatory and promote a neurotoxic environment resulting in neurodegeneration.

“Understanding the underlying molecular mechanisms and identifying these genetic factors has implications for evaluating stress-related risk/progression to neurodegeneration, informing the success of interventions based on stress management and potential risks associated with the common use of glucocorticoids.”

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