A new study uncovers a lung–brain pathway linking smoking to neurodegeneration

Researchers have long known that smoking is associated with neurodegenerative diseases. A 2011 study showed that heavy smoking in midlife more than doubled the risk of dementia, including Alzheimer’s and vascular dementia, decades later.

However, dementia has been less studied in smokers, partly because it develops later in life, while smokers often have shorter lifespans.

Traditionally, scientists have explained this connection through damage to the vascular and respiratory systems, which reduces oxygen supply to the brain over time. But a new study from the University of Chicago, published in *Science Advances*, suggests a different mechanism involving communication between the lungs and the brain.

The researchers identified a previously unknown pathway driven by pulmonary neuroendocrine cells (PNECs). When exposed to nicotine, these cells release exosomes—tiny vesicles carrying biological material—that interfere with iron balance in neurons. This disruption triggers changes commonly seen in neurodegenerative conditions.

According to the authors, this “lung–brain axis” provides a new explanation for how smoking contributes to cognitive decline. It also highlights the role of the lungs as an active signaling organ that can influence brain health, rather than merely being damaged by smoke.

Because natural PNECs are extremely rare, the team created induced PNECs from human stem cells to study them in the laboratory. They found that nicotine exposure led these cells to release large amounts of exosomes rich in serotransferrin, a protein involved in iron transport.

This process may send misleading signals through the vagus nerve, altering iron regulation in the brain. The resulting imbalance can cause oxidative stress, mitochondrial dysfunction, and increased levels of proteins linked to neurodegeneration. It may also trigger ferroptosis—a form of cell death associated with Alzheimer’s and Parkinson’s disease.

Although it remains unclear whether this mechanism directly causes dementia, the findings significantly advance understanding of how smoking affects the body. Future research will explore whether blocking these exosomes could offer new therapeutic strategies.