Traffic-related air pollutants (TRAP-PM) promote neuronal amyloidogenesis through oxidative damage to lipid rafts.

Traffic-related air pollution particulate matter (TRAP-PM) is associated with increased risk of Alzheimer Disease (AD). Rodent models respond to nano-sized TRAP-PM (nPM) with increased production of amyloid Aß peptides, concurrently with oxidative damage. Because pro-Aß processing of the amyloid precursor protein (APP) occurs on subcellular lipid rafts, we hypothesized that oxidative stress from nPM exposure would alter lipid rafts to favor Aß production. This hypothesis was tested with J20 mice and N2a cells transgenic for hAPPswe (familial AD). Exposure of J20-APPswe mice to nPM for 150 h caused increased lipid oxidation (4-HNE) and increased the pro-amyloidogenic processing of APP in lipid raft fractions in cerebral cortex; the absence of these changes in cerebellum parallels the AD brain region selectivity for Aß deposits. In vitro, nPM induced similar oxidative responses in N2a-APPswe cells, with dose-dependent production of NO, oxidative damage (4-HNE, 3NT), and lipid raft alterations of APP with increased Aß peptides. The antioxidant N-acetyl-cysteine (NAC) attenuated nPM-induced oxidative damage and lipid raft alterations of APP processing. These findings identify neuronal lipid rafts as novel targets of oxidative damage in the pro-amyloidogenic effects of air pollution.

Exposures of elderly volunteers with and without chronic obstructive pulmonary disease (COPD) to concentrated ambient fine particulate pollution.

The elderly and individuals who have chronic obstructive pulmonary disease (COPD) may be sensitive to particulate matter (PM) air pollution. We evaluated short-term health responses of 13 elderly volunteers with COPD and 6 age-matched healthy adults to controlled exposures of ambient PM pollution in suburban Los Angeles. Using a Harvard particle concentrator and a whole-body chamber, we exposed each person on separate occasions to approximately 200 microg/m(3) concentrated ambient particles (CAP) less than 2.5 mum in diameter and to filtered air (FA). Each exposure lasted 2 h with intermittent mild exercise. We found no significant effects of CAP on symptoms, spirometry, or induced sputum. A significant negative effect of CAP on arterial oxygenation (measured by pulse oximetry) immediately postexposure was more pronounced in healthy subjects. Peripheral blood basophils increased after CAP in healthy but not in COPD subjects. In both groups, red cell counts increased slightly 1 day after exposure to FA but not to CAP. Preexposure ectopic heartbeats were infrequent in healthy subjects, but increased modestly during/after CAP exposure relative to FA. Ectopic beats were more frequent in COPD subjects, but decreased modestly during/after CAP relative to FA. Heart-rate variability over multi-hour intervals was lower after CAP than after FA in healthy elderly subjects but not in COPD subjects. Thus, in this initial small-scale study of older volunteers experimentally exposed to ambient PM, some acute cardiopulmonary responses were consistent with effects reported from epidemiologic studies. Unexpectedly, individuals with COPD appeared less susceptible than healthy elderly individuals. Further investigation of older adults is warranted to understand the pathophysiology and public health significance of these findings.