Chronic stress, which involves a pathway called the hypothalamic-pituitary-adrenal (HPA) axis, may contribute to the development of Alzheimer’s disease, according to a new review paper.
Armstrong et al. summarize the literature describing environmental and genetic factors that can impact an individual’s HPA axis reactivity and function and ultimately Alzheimer’s disease risk. Image credit: National Institute on Aging / National Institutes of Health.
“Chronic psychosocial stress is increasingly being recognized as a risk factor for sporadic Alzheimer’s disease,” said Dr. David Groth, a researcher in the Curtin Health Innovation Research Institute and the Curtin Medical School at Curtin University, and his colleagues.
“The 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 Alzheimer’s patients and make a major contribution to the disease process.”
“The underlying mechanisms remain poorly understood,” they said.
“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 Alzheimer’s disease.”
In their review paper, the authors described how environmental and genetic factors can impact individuals’ HPA axis, and ultimately their risk of Alzheimer’s disease.
They also proposed a mechanism by which genetic factors that influence the HPA axis may also affect inflammation, a key driver of neurodegeneration.
“What we know is that chronic stress does affect many biological pathways within our body,” Dr. Groth said.
“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 paper was published in the journal Biological Reviews.
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Ayeisha Milligan Armstrong et al. Chronic stress and Alzheimer’s disease: the interplay between the hypothalamic-pituitary-adrenal axis, genetics and microglia. Biological Reviews, published online June 22, 2021; doi: 10.1111/brv.12750
