Long before the brain undergoes a level of degeneration that destroys precious memories, the body could be crying for help.
Elevated levels of a hormone called growth/differentiation factor–15 (GDF15) in the peripheral blood were associated with dementia risk in a recent study, with researchers arguing the chemical could serve as a handy biomarker for future cognitive decline.
A large international team of researchers led by scientists from the US National Institute on Aging used data on a comprehensive map of human proteins from six different studies to characterize the connection between GDF15 and dementia, and to propose processes by which it could contribute to neurodegeneration.
Their findings, based on up to a decade of data on around half a million individuals, suggest that people with higher levels of the growth factor are significantly more likely to develop dementia.
The association was strongest between GDF15 and vascular dementia, a form of neurodegeneration caused by a reduced blood flow to the nervous system.
GDF15 has been suspected of playing a role in a range of health conditions, including kidney disease and severe morning sickness. Some research has implicated the hormone in accelerated cognitive decline, though its value in predicting dementia hasn’t been clear.
The team found that the growth factor is expressed in a wide variety of tissues, largely in the kidney, bladder, and the brain’s ventricles. Curiously, they found little sign that it was made by cells within the central nervous system itself.
The researchers also found GDF15 increases gradually with both chronological and biological age, especially among males.
Crucially, higher levels of the hormone were associated with an increased risk of dementia, even after adjusting for demographics and multiple health conditions. Expanding their research to include plasma from participants of a slightly younger age, the team found a doubling of GDF15 in middle age predicted a 55% increased chance of developing dementia over the next 20 years.
Laboratory studies on immune cells exposed to the growth factor revealed changes in metabolism and antiviral signaling that could influence the health of brain tissue in a variety of ways.
“Circulating GDF15 abundance correlates with molecular changes that can be protective in some contexts – such as suppressing cancer cell proliferation,” the team writes. “However, our cohort analyses and two-sample MR support the idea that, in dementia, GDF15’s immunosuppressive effects may instead contribute to a pathogenic process.”
The researchers note that limitations in the study leave the door open for further research on GDF15’s presence in spinal fluid and its effects on specialized immune cells in the nervous system.
But the hormone is also looking like a strong contender for early diagnostic tools for dementia that could help specialists put the brakes on the condition’s development, if not prepare individuals for the challenges that lie ahead.
This research was published in Science Advances.
Source: National Institute on Aging via MedicalXpress
Fact-checked by Bronwyn Thompson
