2026-04-10 シカゴ大学（UChicago）
A new study from the lab of Asst. Prof. Joyce Chen at the University of Chicago Pritzker School of Molecular Engineering suggests a new reason why heavy midlife smoking can double the risk of dementia later in life.Copyright Shutterstock.com
＜関連情報＞
- https://news.uchicago.edu/story/smoking-may-spark-lung-brain-reaction-tied-dementia-study-finds
- https://www.science.org/doi/10.1126/sciadv.ady2696
肺神経内分泌細胞由来のエクソソームは、肺神経細胞における鉄ホメオスタシスと酸化ストレスを調節する Pulmonary neuroendocrine cell–derived exosomes regulate iron homeostasis and oxidative stress in lung neurons
Abhimanyu Thakur, Kui Zhang, Jonathan Chen, Shuya Mei, […] , and Huanhuan Joyce Chen
Science Advances Published:8 Apr 2026
DOI:https://doi.org/10.1126/sciadv.ady2696
Abstract
Nicotine, the principal addictive component of cigarettes, is linked to cognitive decline and neurodegenerative alterations, likely through oxidative stress and impaired iron regulation in neurons. Yet, underlying molecular pathways remain unclear. This study examined the role of pulmonary neuroendocrine cells (PNECs) in smoke-induced neural changes. Using human pluripotent stem cells, we generated induced PNECs (iPNECs) to overcome culture limitations and performed mechanistic analyses. We found that nicotine exposure stimulates iPNECs to secrete exosomes enriched with serotransferrin, an iron-binding glycoprotein. Neurons internalizing these exosomes displayed elevated levels of transferrin receptor 1 (TFR1), divalent metal transporter 1, and duodenal cytochrome b, associated with ferritin accumulation, oxidative stress, and adenosine triphosphate depletion. Inhibition of TFR1 alleviated these effects. Furthermore, nicotine-triggered exosomes increased α-synuclein expression in neurons in a manner consistent with stress- and vulnerability-associated signatures observed in human lungs and nicotine-exposed mice, highlighting PNEC-derived exosomal signaling that may contribute to neuronal dysfunction.
中年期のヘビースモーカーとアルツハイマー病および血管性認知症の長期リスク Heavy Smoking in Midlife and Long-term Risk of Alzheimer Disease and Vascular Dementia
Minna Rusanen, MD; Miia Kivipelto, MD, PhD; Charles P. Quesenberry Jr, PhD;et al
JAMA Internal Medicine Published:February 28, 2011
DOI:10.1001/archinternmed.2010.393
Abstract
Background Smoking is a risk factor for several life-threatening diseases, but its long-term association with dementia is controversial and somewhat understudied. Our objective was to investigate the long-term association of amount of smoking in middle age on the risk of dementia, Alzheimer disease (AD), and vascular dementia (VaD) several decades later in a large, diverse population.
Methods We analyzed prospective data from a multiethnic population-based cohort of 21 123 members of a health care system who participated in a survey between 1978 and 1985. Diagnoses of dementia, AD, and VaD made in internal medicine, neurology, and neuropsychology were collected from January 1, 1994, to July 31, 2008. Multivariate Cox proportional hazards models were used to investigate the association between midlife smoking and risk of dementia, AD, and VaD.
Results A total of 5367 people (25.4%) were diagnosed as having dementia (including 1136 cases of AD and 416 cases of VaD) during a mean follow-up period of 23 years. Results were adjusted for age, sex, education, race, marital status, hypertension, hyperlipidemia, body mass index, diabetes, heart disease, stroke, and alcohol use. Compared with nonsmokers, those smoking more than 2 packs a day had an elevated risk of dementia (adjusted hazard ratio [HR], 2.14; 95% CI, 1.65-2.78), AD (adjusted HR, 2.57; 95% CI, 1.63-4.03), and VaD (adjusted HR, 2.72; 95% CI, 1.20-6.18).
Conclusions In this large cohort, heavy smoking in midlife was associated with a greater than 100% increase in risk of dementia, AD, and VaD more than 2 decades later. These results suggest that the brain is not immune to long-term consequences of heavy smoking.
