Exposure to particulate matter (PM) in the ambient air and its interactions with APOE alleles may contribute to the acceleration of brain aging and the pathogenesis of Alzheimer's disease (AD). Neurodegenerative effects of particulate air pollutants were examined in a US-wide cohort of older women from the Women's Health Initiative Memory Study (WHIMS) and in experimental mouse models. Residing in places with fine PM exceeding EPA standards increased the risks for global cognitive decline and all-cause dementia respectively by 81 and 92%, with stronger adverse effects in APOE ɛ4/4 carriers. Female EFAD transgenic mice (5xFAD+/−/human APOE ɛ3 or ɛ4+/+) with 225 h exposure to urban nanosized PM (nPM) over 15 weeks showed increased cerebral β-amyloid by thioflavin S for fibrillary amyloid and by immunocytochemistry for Aβ deposits, both exacerbated by APOE ɛ4. Moreover, nPM exposure increased Aβ oligomers, caused selective atrophy of hippocampal CA1 neurites, and decreased the glutamate GluR1 subunit. Wildtype C57BL/6 female mice also showed nPM-induced CA1 atrophy and GluR1 decrease. In vitro nPM exposure of neuroblastoma cells (N2a-APP/swe) increased the pro-amyloidogenic processing of the amyloid precursor protein (APP). We suggest that airborne PM exposure promotes pathological brain aging in older women, with potentially a greater impact in ɛ4 carriers. The underlying mechanisms may involve increased cerebral Aβ production and selective changes in hippocampal CA1 neurons and glutamate receptor subunits.

An emerging hypothesis in the field of air pollution is that oxidative stress is one of the important pathways leading to adverse health effects of airborne particulate matter (PM). To advance our understanding of sources and chemical elements contributing to aerosol oxidative potential and provide global comparative data, we report here on the biological oxidative potential associated with size-segregated airborne PM in different urban areas of the world, measured by a biological (cell-based) reactive oxygen species (ROS) assay. Our synthesis indicates a generally greater intrinsic PM oxidative potential as well as higher levels of exposure to redox-active PM in developing areas of the world. Moreover, on the basis of our observations, smaller size fractions are generally associated with higher intrinsic ROS activity compared with larger PM size fractions. Another important outcome of our study is the identification of major species and sources that are associated with ROS activity. Water-soluble transition metals (e.g., Fe, Ni, Cu, Cr, Mn, Zn and V) and water-soluble organic carbon (WSOC) showed consistent correlations with the oxidative potential of airborne PM across different urban areas and size ranges. The major PM sources associated with these chemical species include residual/fuel oil combustion, traffic emissions, and secondary organic aerosol formation, indicating that these sources are major drivers of PM-induced oxidative potential. Moreover, comparison of ROS activity levels across different seasons indicated that photochemical aging increases the intrinsic oxidative potential of airborne PM.

The recent economic crisis in Greece resulted in a serious wintertime air pollution episode in Thessaloniki. This air quality deterioration was mostly due to the increased price of fuel oil, conventionally used as a source of energy for domestic heating, which encouraged the residents to burn the less expensive wood/biomass during the cold season. A wintertime sampling campaign for fine particles (PM2.5) was conducted in Thessaloniki during the winters of 2012 and 2013 in an effort to quantify the extent to which the ambient air was impacted by the increased wood smoke emissions. The results indicated a 30% increase in the PM2.5 mass concentration as well as a 2-5-fold increase in the concentration of wood smoke tracers, including potassium, levoglucosan, mannosan, and galactosan. The concentrations of fuel oil tracers (e.g., Ni and V), on the other hand, declined by 20-30% during 2013 compared with 2012. Moreover, a distinct diurnal variation was observed for wood smoke tracers, with significantly higher concentrations in the evening period compared with the morning. Correlation analysis indicated a strong association between reactive oxygen species (ROS) activity and the concentrations of levoglucosan, galactosan, and potassium, underscoring the potential impact of wood smoke on PM-induced toxicity during the winter months in Thessaloniki.

The increasing popularity of electronic cigarettes (e-cigarettes) and, more recently, the new "heatnot-burn" tobacco products (iQOS) as alternatives to traditional tobacco cigarettes has necessitated further documentation of and research into the composition and potential health risks/benefits of these devices. In a recent study, we compared second-hand exposure to particulate metals and organic compounds from e-cigarettes and traditional cigarettes, by conducting continuous and time-integrated measurements in an indoor environment, followed by computing the emission rates of these species using a single-compartment mass balance model. In this study, we have used a similar approach to further expand our previous analyses by characterizing black carbon, metal particles, organic compounds, and size-segregated particle mass and number concentrations emitted from these devices in addition to the newly marketed iQOS. Analysis of the iQOS sidestream smoke indicated that the particulate emission of organic matter from these devices is significantly different depending on the organic compound. While polycyclic aromatic hydrocarbons (PAHs) were mostly non-detectable in the iQOS smoke, certain n-alkanes, organic acids (such as suberic acid, azelaic acid, and n-alkanoic acids with carbon numbers between 10 and 19) as well as levoglucosan were still emitted in substantial levels from iQOS (up to 2-6 mg/h during a regular smoking regimen). Metal emissions were reduced in iQOS smoke compared to both electronic cigarettes and conventional cigarettes and were mostly similar to the background levels. Another important finding is the presence of carcinogenic aldehyde compounds, including formaldehyde, acetaldehyde, and acrolein, in iQOS smoke, although the levels were substantially lower compared to conventional cigarettes. EDITORYifang Zhu

Background:Rodent models for urban air pollution show consistent induction of inflammatory responses in major brain regions. However, the initial impact of air pollution particulate material on olfactory gateways has not been reported.Objective:We evaluated the olfactory neuroepithelium (OE) and brain regional responses to a nanosized subfraction of urban traffic ultrafine particulate matter (nPM, < 200 nm) in vivo, ex vivo, and in vitro.Methods:Adult mice were exposed to reaerosolized nPM for 5, 20, and 45 cumulative hours over 3 weeks. The OE, the olfactory bulb (OB), the cerebral cortex, and the cerebellum were analyzed for oxidative stress and inflammatory responses. Acute responses of the OE to liquid nPM suspensions were studied with ex vivo and primary OE cultures.Results:After exposure to nPM, the OE and OB had rapid increases of 4-hydroxy-2-nonenal (4-HNE) and 3-nitrotyrosine (3-NT) protein adducts, whereas the cerebral cortex and cerebellum did not respond at any time. All brain regions showed increased levels of tumor necrosis factor-α (TNFα) protein by 45 hr, with earlier induction of TNFα mRNA in OE and OB. These responses corresponded to in vitro OE and mixed glial responses, with rapid induction of nitrite and inducible nitric oxide synthase (iNOS), followed by induction of TNFα.Conclusions:These findings show the differential time course of oxidative stress and inflammatory responses to nPM between the OE and the brain. Slow cumulative transport of inhaled nPM into the brain may contribute to delayed responses of proximal and distal brain regions, with potential input from systemic factors.Citation:Cheng H, Saffari A, Sioutas C, Forman HJ, Morgan TE, Finch CE. 2016. Nanoscale particulate matter from urban traffic rapidly induces oxidative stress and inflammation in olfactory epithelium with concomitant effects on brain. Environ Health Perspect 124:1537–1546; http://dx.doi.org/10.1289/EHP134

BackgroundExposure to traffic-related air pollution (TRAP) is associated with accelerated cognitive aging and higher dementia risk in human populations. Rodent brains respond to TRAP with activation of astrocytes and microglia, increased inflammatory cytokines, and neurite atrophy. A role for Toll-like receptor 4 (TLR4) was suggested in mouse TLR4-knockouts, which had attenuated lung macrophage responses to air pollution.MethodsTo further analyze these mechanisms, we examined mixed glial cultures (astrocytes and microglia) for RNA responses to nanoscale particulate matter (nPM; diameter <0.2 μm), a well-characterized nanoscale particulate matter subfraction of TRAP collected from a local freeway (Morgan et al. Environ Health Perspect 2011; 119,1003–1009, 2011). The nPM was compared with responses to the endotoxin lipopolysaccharide (LPS), a classic TLR4 ligand, using Affymetrix whole genome microarray in rats. Expression patterns were analyzed by significance analysis of microarrays (SAM) for fold change and by weighted gene co-expression network analysis (WGCNA) to identify modules of shared responses between nPM and LPS. Finally, we examined TLR4 activation in hippocampal tissue from mice chronically exposed to nPM.ResultsSAM and WGCNA analyses showed strong activation of TLR4 and NF-κB by both nPM and LPS. TLR4 siRNA attenuated TNFα and other inflammatory responses to nPM in vitro, via the MyD88-dependent pathway. In vivo, mice chronically exposed to nPM showed increased TLR4, MyD88, TNFα, and TNFR2 RNA, and decreased NF-κB and TRAF6 RNA TLR4 and NF-κB responses in the hippocampus.ConclusionsThese results show TLR4 activation is integral in brain inflammatory responses to air pollution, and warrant further study of TLR4 in accelerated cognitive aging by air pollution.Electronic supplementary materialThe online version of this article (doi:10.1186/s12974-017-0858-x) contains supplementary material, which is available to authorized users.

A year-long sampling campaign of quasi-ultrafine particles (dp < 0.25 μm) was conducted at 10 distinct sites representing source, urban and/or near-freeway, rural receptor and desert locations across the Los Angeles air basin. Redox activity of the PM samples was measured by means of the Dithiothreitol (DTT) assay and detailed chemical analysis was performed to measure the concentrations of chemical species. DTT activity per unit air volume and unit PM mass (expressed in nmol min(-1) m(-3) and nmol/min/μg PM, respectively) showed similar trends across sites and seasons. DTT activity was generally higher during cold seasons (winter and fall) compared to warm seasons (summer and spring). Noticeable peaks were observed at urban near-freeway locations representing "source" sites impacted by fresh traffic emissions. Regression analysis indicated strong association (R > 0.7) between the DTT activity and the concentrations of carbonaceous species (OC, EC, WSOC and WIOC) across all seasons and strong winter-time correlations with organic tracers of primary vehicular emissions including polycyclic aromatic hydrocarbons (PAHs), alkanes, hopanes and steranes. Strong correlations were also observed, particularly during winter, between DTT activity and transition metals (e.g., Cr, Mn, V, Fe, Cu, Cd and Zn), which share similar vehicular sources with primary organics. A multivariate linear regression analysis indicated that the variability in DTT activity is best explained by the variability in concentrations of WSOC, WIOC, EC and hopanes. Combined contributions from these species explained 88% of the DTT activity. The appearance of WSOC as a typical tracer of secondary organic aerosol, along with EC, WIOC and hopanes, all markers of emissions from primary combustion sources, emphasizes the contributions of both primary and secondary sources to the overall oxidative potential of quasi-ultrafine particles. Supplemental materials are available for this article. Go to the publisher's online edition of the Journal of Environmental Science and Health, Part A, to view the supplemental file.

To identify major sources of ambient fine particulate matter (PM 2.5 , dp < 2.5 µm) and quantify their contributions in the state of California, a positive matrix factorization (PMF) receptor model was applied on Speciation Trends Network (STN) data, collected between 2002 and 2007 at eight distinct sampling locations, including El Cajon, Rubidoux, Los Angeles, Simi Valley, Bakersfield, Fresno, San Jose, and Sacramento. Between five to nine sources of fine PM were identified at each sampling site, several of which were common among multiple locations. Secondary aerosols, including secondary ammonium nitrate and ammonium sulfate, were the most abundant contributor to ambient PM 2.5 mass at all sampling sites, except for San Jose, with an annual average cumulative contribution of 26 to 63 %, across the state. On an annual average basis, vehicular emissions (including both diesel and gasoline vehicles) were the largest primary source of fine PM at all sampling sites in southern California (17-18 % of total mass), whereas in Fresno and San Jose, biomass burning was the most dominant primary contributor to ambient PM 2.5 (27 and 35 % of total mass, respectively), in general agreement with the results of previous source apportionment studies in California. In Bakersfield and Sacramento, vehicular emissions and biomass burning displayed relatively equal annual contributions to ambient PM 2.5 mass (12 and 25 %, respectively). Other commonly identified sources at all sites included aged and fresh sea salt and soil, which contributed to 0.5-13 %, 2-27 %, and 1-19 % of the total mass, respectively, across all sites and seasons. In addition, a few minor sources were identified exclusively at some of the sites (e.g., chlorine sources, sulfate-bearing road dust, and different types of industrial emissions). These sources overall accounted for a small fraction of the total PM mass across the sampling locations (1 to 15 %, on an annual average basis).