Air Pollution and Alzheimer’s Disease
Project Collaborators:
- Dr. Deborah Cory-Slechta
- Dr. Christopher Higgins
- Dr. M. Kerry O'Banion
- Dr. Günter Oberdörster
- Dr. James Ranville Colorado School of Mines
Proposed pathways by which inhaled nanoscale particles (engineered or
combustion-derived from ambient air) can travel to the brain.
Adverse effects in the respiratory tract and cardiovascular system following exposures to ambient air pollution have been recognized for decades, particularly in those individuals who are made more susceptible due to underlying disease. Mounting evidence suggests that the central nervous system (CNS) is also vulnerable to the adverse health effects that are associated with air pollution. Chronic oxidative stress and inflammation are thought to underlie the respiratory and cardiovascular effects that have been observed, so such processes may also be responsible for the CNS effects. These processes are also linked to neurodegenerative disorders, like Alzheimer’s disease (AD). We hypothesize that exposure to ambient air pollution particulate matter, more specifically to ultrafine particles, is causally related to the persistent stress and inflammatory reactions due to the ability of these tiny particles to gain access via olfactory transport and by crossing the blood-brain barrier to the brain. Using a mouse model of AD, we are conducting exposures to concentrated ambient ultrafine particles and to laboratory-generated tracer particles to:
Deposition of inhaled particulates in different regions
of the respiratory tract according to the ICRP model.
- Understand the routes and kinetics of uptake, delivery, and clearance of nanoscale particles in the CNS
- Document changes in innate immune cell activation status and the onset and progression of AD-related pathology
- Examine changes in learning and memory in the mice following exposure
- Examine the role that tumor necrosis factor plays in these responses
The outcomes from these studies will help us to better understand the risk factors that contribute to the onset and development of neurodegeneration in the human population.