Part of the problem in finding a cure for Alzheimer's disease is there's still so much about the disease that we don't fully understand – including exactly how and why it gets started in the brain. Now a new study suggests chronic stress might play an important role in the process.
The research focuses on the hypothalamic-pituitary-adrenal axis (HPA axis), a pathway that links two parts of the brain with glands located just above the kidneys. The HPA axis controls a variety of biological processes and helps manage our reaction to stress.
In a review of previous studies, researchers explore how chronic stress is increasingly being linked to Alzheimer's, suggesting that managing stress levels earlier in life could be one way of reducing the risk of developing neurodegenerative diseases later on.
"What we know is that chronic stress does affect many biological pathways within our body," says molecular geneticist David Groth from Curtin University in Australia.
"There is an intimate interplay between exposure to chronic stress and pathways influencing the body's reaction to such stress."
Part of the job of the HPA axis is to regulate the release of the steroid hormone cortisol: the greater the stress, the more cortisol is released. The hormone, part of a class known as glucocorticoid hormones, increases blood sugar and suppresses the immune system.
Disruption of the HPA axis, and subsequent increases in cortisol levels, are often seen in Alzheimer's cases. However, exactly why this is – and what genetic or environmental factors might contribute to it – isn't something scientists have fully figured out.
In the study, the researchers suggest that genetic factors impacting the HPA axis might also affect inflammation in the brain, which is known to contribute to neuron damage seen in diseases such as Alzheimer's.
"Genetic variations within these pathways can influence the way the brain's immune system behaves leading to a dysfunctional response," says Groth.
"In the brain, this leads to a chronic disruption of normal brain processes, increasing the risk of subsequent neurodegeneration and ultimately dementia."
Specifically, the team hypothesizes that chronic stress could trigger a glucocorticoid response that primes the microglia – the brain's immune cells – to become more inflammatory, increasing the risk of neurodegeneration.
Genetic variations in how the HPA axis reacts to stress could be key in how severe this microglia inflammatory reaction actually is, the researchers suggest. More work is going to be needed to identify what those variations are, but it's a starting point.
What we do know about Alzheimer's is that some of the signs of it can start appearing many years in advance, and that could give scientists a valuable opportunity to stop or to limit the disease's development – something this new study should help with.
"Identifying the molecular mechanisms underlying the association between chronic stress and Alzheimer's disease, as well as identifying genetic factors that could contribute to the susceptibility of this association, may allow for new therapeutic targets to be identified as well as strategies targeting chronic stress management to be implemented," the researchers write in their paper.
The research has been published in Biological Reviews.