Decades of research have suggested that people who start to lose their hearing as they grow older are more likely to develop Alzheimer’s disease. Why that happens isn’t fully understood. Struggling to hear can make people less sociable perhaps, and increased long-term workload in the parts of the brain that deal with hearing might weaken cognitive performance elsewhere.

A recent study now unpacks one molecular mechanism that seems to have an important role in the interplay between hearing loss and the development of Alzheimer’s—at least in mice. The research tracks the patterns of gene and protein expression of a protein called GDF1. Increasing levels of this molecule can mitigate the symptoms of dementia in the animals. That might offer a new route to tackle the disease in people.

“We believe this is a significant finding,” says paper coauthor Zhentao Zhang, a neurologist at Renmin Hospital of Wuhan University, China. “GDF1 may represent a therapeutic target for Alzheimer’s disease.” The study was published in Nature Aging.

Working with transgenic mice bred to emulate the signs of Alzheimer’s disease, the researchers examined what happened in brains of the animals made deaf by surgery. They found that their deafness led to greater deposits of amyloid-β plaques—a signature pathology of Alzheimer’s—in the hippocampus, auditory cortex, and temporal association cortex. The loss of hearing was also associated with poor cognitive performance among the mice, based on maze tests, as well as decreased synaptic density in the hippocampus.

The study then analyzed the possible underlying mechanisms by elucidating patterns of gene expression in the deaf mice. They found significant down-regulation of the gdf1 gene, which led to lower levels of the growth factor GDF1. Subsequent experiments confirmed the apparent role of GDF1, demonstrating how supplements of the protein could ameliorate the cognitive impairment, amyloid burden, and synaptic dysfunction induced by hearing loss.

And reducing levels of the protein in nondeaf mice mimicked the effects of hearing loss— including synaptic degeneration, plaque accumulation, and impaired cognition in maze tests. “Knockdown of GDF1 mimics the detrimental effect of hearing loss on cognition, while overexpression of GDF1 in the hippocampus attenuates the cognitive impairment induced by deafness,” Zhang says. “These findings indicate that hearing loss could promote pathological changes in Alzheimer’s disease by inhibiting the GDF1 signaling pathway.”

Hearing loss does not directly cause Alzheimer’s, emphasizes ear, nose, and throat expert Hong-Bo Zhao, while noting the potential significance of the findings. “This is a strong paper and provides solid experimental evidence that hearing loss can promote Alzheimer’s disease,” says Zhao, who’s at the Yale University School of Medicine in New Haven, Connecticut. “That is, hearing loss can exacerbate and aggravate Alzheimer’s disease development progression.”

The association between hearing loss and Alzheimer’s appears to go both ways. Zhao’s lab showed in 2020 how the early stages of the disease in Alzheimer’s mice models can cause changes to hearing that can be tracked to diagnose and follow the progression of the dementia.

Focusing on GDF1 as a way to treat the disease in people is “potentially possible,” he adds. “There is already evidence indicating that using hearing aids or cochlear implant can prevent cognitive decline in Alzheimer’s disease patients.”

Zhang’s team is now working to determine the exact molecular mechanisms that underlie the neuroprotective effects of GDF1. “We also aim to determine how hearing loss modifies the function of the central nervous system,” he says.

Article originally appeared on PNAS