University of Chicago Study Uncovers Novel Lung-Brain Signaling Pathway Linking Nicotine to Neurodegeneration

UChicago researchers discover that nicotine causes lung cells to release exosomes that disrupt brain iron levels, providing a new link to dementia and Alzheimer's.

By: AXL Media

Published: Apr 9, 2026, 4:06 AM EDT

Source: Information for this report was sourced from University of Chicago and Science Advances

Unveiling the Active Signaling Role of the Human Lung

For decades, the medical community viewed the lungs as passive victims of tobacco smoke, suffering respiratory and vascular damage that indirectly starved the brain of oxygen. However, new research from the University of Chicago Pritzker School of Molecular Engineering reveals that the lung is an active signaling organ capable of influencing brain pathology directly. By mapping a previously unknown communication route, scientists have demonstrated how nicotine-induced signals travel from the respiratory system to the mind, establishing a "lung-brain" axis. This discovery provides a biological explanation for why heavy midlife smoking is associated with a 100% increase in the risk of developing dementia later in life.

The Discovery of Pulmonary Neuroendocrine Cell Communication

The study focuses on Pulmonary Neuroendocrine Cells (PNECs), unique airway sensors that constitute less than 1% of lung tissue. Because these cells are extremely rare and difficult to isolate, the research team used human pluripotent stem cells to generate large quantities of induced PNECs (iPNECs) for laboratory study. When these cells were exposed to nicotine, they reacted by emitting massive quantities of exosomes—microscopic particles that carry biological instructions between organs. According to postdoctoral researcher Kui Zhang, the study's co-first author, these exosomes act as a primary vehicle for smoke-induced damage, transporting harmful signals that eventually bypass standard regulatory pathways.

Disrupting Iron Homeostasis and Neuronal Health

The specific exosomes triggered by nicotine are notably rich in serotransferrin, a protein essential for regulating iron flow in the bloodstream. When these particles reach the brain, they provide the body with incorrect instructions, leading to a perturbation of iron homeostasis within neurons. This iron imbalance is a known driver of oxidative stress and mitochondrial dysfunction, both of which are central hallmarks of neurodegenerative disease. Assistant Professor Joyce Chen, the study's corresponding author, noted that this process also increases the expression of α-synuclein, a protein closely linked to the progression of Parkinson’s and other cognitive disorders.