We propose that urban traffic-derived nano-sized particulate matter (nPM, <0.1 um) in urban air pollution is a risk factor in AD by promoting amyloidogenesis. These experiments examine nPM induced ROS and pro-amyloidogenic APP processing.
In the search for environmental factors in AD risk and progression, more than five epidemiological studies have associated premature cognitive declines with air pollutants. Correspondingly, rodent models in ours and two other labs show increased Aβ in response to selected air pollutants. Because nPM increases ROS and Aβ, and because H2O2 can induce Aβ production, we will evaluate the relationships of Abeta and to oxidative stress in responses to nPM. We focus on the olfactory neuroepithelium (O-NE), the initial neuronal contact with air pollutants, and the olfactory bulb (OB) which receives O-NE projections. In vivo, mice are given time-and dose controlled exposure to nPM, followed by analysis of O-NE and OB. In vitro, the O-NE will be exposed to nPM, in comparison with N2a cells carrying the swe-APP mutation which respond to nPM with increased Aβ. We also examine the potential of mitochondrial catalase (mCAT) for attenuating nPM induced Aβ and ROS.