A new study from the University of Chicago has found that smoking can raise dementia risk by triggering harmful chemical signals from the lungs to the brain. The researchers have pointed out to nicotine-triggered miscommunication.
The findings of the study have been published in Science Advances journal.
“It reveals that the lung is not just a passive target of smoke exposure, but an active signaling organ influencing brain pathology,” said the paper’s corresponding author Asst. Prof. Joyce Chen, from UChicago’s Pritzker School of Molecular Engineering (UChicago PME) and the Ben May Department for Cancer Research.
The researchers found a previously unmapped route from the lungs to the mind through pulmonary neuroendocrine cells (PNECs). When exposed to nicotine, these cells release exosomes—tiny particles that transport cellular products and waste—that disrupt the iron balance in neurons, triggering symptoms often found in dementia patients.
TOI Health connected with Asst. Prof. Joyce Chen regarding the study and to understand how smoking triggers dementia risk in individuals.
How does nicotine trigger miscommunication between the lung and the brain?
Joyce Chen: Nicotine stimulates lung neuroendocrine cells to release exosomes that disrupt iron balance. Vagal nerves, which control involuntary movements like breathing, heartbeats and digestion, carry this signal back to the brain, where it creates an iron imbalance in the brain’s neurons. This iron imbalance drives many disorders that are hallmarks of neurodegenerative disease. A second possibility is that these exosomes may travel directly through the bloodstream and reach the brain, potentially crossing the blood–brain barrier and acting on brain cells more directly. Together, these findings suggest that the lung is not just a passive target of nicotine exposure, but an active signaling organ that can influence brain health. However, these causal relationships still need to be carefully tested in future studies.
What are PNECs and what is their importance?
Joyce Chen: Pulmonary neuroendocrine cells (PNECs) are rare, specialized cells in the airway that act as sensors of the lung environment. Despite their importance, they are difficult to study because they are extremely rare, accounting for only about 1% of lung epithelial cells.Nicotine triggers PNECs to release a huge amount of an exosome which carries a protein the body uses to regulate iron. Our research at the UChicago Pritzker School of Molecular Engineering described a previously unrecognized airway–brain communication pathway that carries this signal from the lungs to the brain, where it creates an iron imbalance in previously healthy neurons.
Does occasional smoking have a similar link to dementia risk?
Joyce Chen: This study highlights that environmental exposures such as nicotine may influence brain health through unexpected biological routes. It also reinforces the importance of reducing all nicotine exposure, particularly in younger populations whose neural systems are still developing.
What would you say to regular smokers with such a health risk looming at the back?
Joyce Chen: Lung structures are so beautiful, but yet so complex. Because of these complexities, diseases can happen in different locations of the lung system, and we have to apply different strategies to study and prevent each of them. But one strategy has been shown time and again to vastly reduce the risk of many lung-related ailments, from cancer and emphysema to dementia: Quit smoking.
