Diesel engine exhaust accelerates plaque formation in a mouse model of Alzheimer’s disease

Abstract

BackgroundIncreasing evidence from toxicological and epidemiological studies indicates that the central nervous system is an important target for ambient air pollutants. We have investigated whether long-term inhalation exposure to diesel engine exhaust (DEE), a dominant contributor to particulate air pollution in urban environments, can aggravate Alzheimer’s Disease (AD)-like effects in female 5X Familial AD (5XFAD) mice and their wild-type female littermates. Following 3 and 13 weeks exposures to diluted DEE (0.95 mg/m3, 6 h/day, 5 days/week) or clean air (controls) behaviour tests were performed and amyloid-β (Aβ) plaque formation, pulmonary histopathology and systemic inflammation were evaluated.ResultsIn a string suspension task, assessing for grip strength and motor coordination, 13 weeks exposed 5XFAD mice performed significantly less than the 5XFAD controls. Spatial working memory deficits, assessed by Y-maze and X-maze tasks, were not observed in association with the DEE exposures. Brains of the 3 weeks DEE-exposed 5XFAD mice showed significantly higher cortical Aβ plaque load and higher whole brain homogenate Aβ42 levels than the clean air-exposed 5XFAD littermate controls. After the 13 weeks exposures, with increasing age and progression of the AD-phenotype of the 5XFAD mice, DEE-related differences in amyloid pathology were no longer present. Immunohistochemical evaluation of lungs of the mice revealed no obvious genetic background-related differences in tissue structure, and the DEE exposure did not cause histopathological changes in the mice of both backgrounds. Luminex analysis of plasma cytokines demonstrated absence of sustained systemic inflammation upon DEE exposure.ConclusionsInhalation exposure to DEE causes accelerated plaque formation and motor function impairment in 5XFAD transgenic mice. Our study provides further support that the brain is a relevant target for the effects of inhaled DEE and suggests that long-term exposure to this ubiquitous air pollution mixture may promote the development of Alzheimer’s disease.

Particulate matter and episodic memory decline mediated by early neuroanatomic biomarkers of Alzheimer’s disease

“…However, this interesting hypothesis was not supported by the neurotoxicological data showing that diesel engine exhaust accelerated amyloid-β plaque formation, with no overt deficits in spatial memory (Hullmann et al, 2017). In contrast, we had previously reported that residing in locations with high PM 2.5 exposure was associated with clinically significant cognitive impairment and dementia among non-Hispanic white older women WHIMS (Cacciottolo et al, 2017).…”

Predisposition to Alzheimer’s and Age-Related Brain Pathologies by PM2.5 Exposure: Perspective on the Roles of Oxidative Stress and TRPM2 Channel

“…Another recent study using 10-week-old female 5xFAD mice reports that exposure to DE (0.95 mg/m 3 , 6 h per day, and 5 days per week) for 3 weeks elevated the levels of cortical Aβ plaque load and whole brain Aβ42 (Hullmann et al, 2017). However, prolonged exposure for 13 weeks resulted in no effect on the levels of Aβ plaque load and whole brain Aβ42, which were already high due to aging and AD progression (Hullmann et al, 2017). Such an observation further indicates an age-related ceiling effect as previously reported in wildtype mice (Woodward et al, 2017).…”

“…The same study also shows that exposure of mouse neuroblastoma N2a cells expressing Swedish mutant APP to 10 µg/ml nPM for 24 h enhanced Aβ42 generation. Another recent study using 10-week-old female 5xFAD mice reports that exposure to DE (0.95 mg/m 3 , 6 h per day, and 5 days per week) for 3 weeks elevated the levels of cortical Aβ plaque load and whole brain Aβ42 (Hullmann et al, 2017). However, prolonged exposure for 13 weeks resulted in no effect on the levels of Aβ plaque load and whole brain Aβ42, which were already high due to aging and AD progression (Hullmann et al, 2017).…”

Coarse particulate matter (PM2.5–10) in Los Angeles Basin air induces expression of inflammation and cancer biomarkers in rat brains

“…Experimentally, it has been shown that prolonged exposures to diesel exhaust cause neuroinflammation in rats 15 , while nanoscale PM from Los Angeles urban traffic induced oxidative stress and inflammation in the olfactory epithelium and the brain 16 . Exposure to vehicle exhaust also increases anxiety and depression-like behaviors in rats 17 , and accelerates plaque formation in a mouse model of Alzheimer’s disease 18 .…”