Research from the University of Chicago has identified a previously unmapped communication route between the lungs and brain that may help explain why heavy smoking in midlife is associated with increased dementia risk. The findings were published in Science Advances
Previous studies have shown that heavy midlife smoking is associated with more than double the risk of dementia, Alzheimer’s disease, and vascular dementia decades later. Whilst most theories focus on smoking’s impact on the vascular and respiratory systems, the new research suggests nicotine-triggered signalling between the lungs and brain may also be involved.
The study focused on pulmonary neuroendocrine cells (PNECs), rare lung cells that combine functions of both nerve and endocrine cells. When exposed to nicotine, these cells release large quantities of exosomes, tiny particles containing biological material, that are rich in serotransferrin, a protein involved in iron regulation.
Researchers generated induced PNECs from human pluripotent stem cells to study these cells, which comprise less than 1% of lung tissue. They found that nicotine exposure caused PNECs to release massive amounts of serotransferrin-rich exosomes, disrupting iron balance in neurons.
According to the corresponding author, Assistant Professor Joyce Chen, this iron imbalance drives oxidative stress, mitochondrial dysfunction, and increased α-synuclein expression—hallmarks of neurodegenerative disease. The disruption can also wrongly trigger ferroptosis, a form of programmed cell death previously associated with both Alzheimer’s and Parkinson’s disease.
The research establishes a clear lung-brain axis, revealing the lung as an active signalling organ rather than merely a passive target of smoke exposure. The team is now investigating whether blocking these exosomes could have therapeutic applications for preventing neurodegeneration.
Source: Medical Xpress / University of Chicago (Science Advances, 2026)
Previous studies have shown that heavy midlife smoking is associated with more than double the risk of dementia, Alzheimer’s disease, and vascular dementia decades later. Whilst most theories focus on smoking’s impact on the vascular and respiratory systems, the new research suggests nicotine-triggered signalling between the lungs and brain may also be involved.
The study focused on pulmonary neuroendocrine cells (PNECs), rare lung cells that combine functions of both nerve and endocrine cells. When exposed to nicotine, these cells release large quantities of exosomes, tiny particles containing biological material, that are rich in serotransferrin, a protein involved in iron regulation.
Researchers generated induced PNECs from human pluripotent stem cells to study these cells, which comprise less than 1% of lung tissue. They found that nicotine exposure caused PNECs to release massive amounts of serotransferrin-rich exosomes, disrupting iron balance in neurons.
According to the corresponding author, Assistant Professor Joyce Chen, this iron imbalance drives oxidative stress, mitochondrial dysfunction, and increased α-synuclein expression—hallmarks of neurodegenerative disease. The disruption can also wrongly trigger ferroptosis, a form of programmed cell death previously associated with both Alzheimer’s and Parkinson’s disease.
The research establishes a clear lung-brain axis, revealing the lung as an active signalling organ rather than merely a passive target of smoke exposure. The team is now investigating whether blocking these exosomes could have therapeutic applications for preventing neurodegeneration.
Source: Medical Xpress / University of Chicago (Science Advances, 2026)
