Inflammation & Alzheimer’s-Like Damage Caused by Severe Air Pollution

Lilian Calderón-Garcidueñas, MD, Ph.D. and James Swenberg, Ph.D.
University of North Carolina at Chapel Hill
T32ES07017 and P30ES10126

Background: Air pollution is a complex mixture of particulate matter, gases, and organic compounds. In controlled exposure studies, ozone and particulate matter have been shown to cause inflammation in the respiratory system as well as increases in circulating levels of inflammatory mediators. Previous research by these investigators has shown that dogs exposed to high levels of air pollution in Mexico City, experienced chronic upper and lower respiratory tract inflammation. The brains of these dogs showed signs of over production of cyclooxygenase-2 (COX2), an enzyme that is known as a mediator of inflammatory responses. The researchers also found accumulation of specific protein fragments that have been implicated in causing adverse effects on neuron function similar to those seen in Alzheimer’s disease. These findings suggested that chronic exposure of humans to air pollution may also cause adverse central nervous system effects.

Advance: To investigate whether air pollution could cause effects in humans similar to those seen in the dogs, these researchers conducted a study using human autopsy samples from the brains of 19 people from Mexico. Some of the people lived in areas of chronically severe air pollution while some lived in areas of low pollution. All of the subjects were non-smokers and had no history of neurological disease or learning abnormalities. The people from cities with severe air pollution had significantly higher COX2 levels in three areas of the brain than did the people from non-polluted areas. The high pollution group also had higher accumulations of harmful proteins in neuronal cells. These findings were very similar to those seen in the dog study.

Implications: The findings of the current study suggest that exposure to high levels of air pollutants is associated with inflammation in the brain and accumulation of toxic proteins. Inflammation and protein accumulation are two causes of neuron dysfunction that show up before classic signs of Alzheimer’s disease in humans. Although this result needs to be confirmed in larger studies, the findings have identified a potential public health risk of great importance. The authors conclude that "The findings suggest a clear need for epidemiological and toxicological studies that can more fully characterize the association between chronic exposure to air pollutants and the risk of developing Alzheimer’s disease.”

Citation: Caldern-Garcidueñas L, Reed W, Maronpot R, Henriquez-Roldan C, Delgado-Chavez R, Calderón-Garcidueñas A, Dragustinovis I, Franco-Lira M, Aragon-Flores M, Solt A, Altenburg M, Torres-Jardon R, Swenberg J. Brain Inflammation and Alzheimer’s-Like Pathology in Individuals Exposed to Severe Air Pollution. Toxicol Pathol. 2004 Nov-Dec;32(6):650-8.