Abstract Ambient particulate matter (PM) air pollution and elevated copper (Cu) exposure are associated with increased Alzheimer’s disease (AD) risk. We hypothesize that inhaled copper-containing ultrafine particles (Cu-UFPs) that model the reactive metal fraction of ambient ultrafine PM (100 nm) translocate from the lungs to distal organs, triggering inflammation and oxidative stress that exacerbate AD-related pathology. This study examined acute pulmonary inflammation and distribution of Cu following short-term inhalation exposures. Male and female APP/PS1 and wild-type (WT) mice were exposed to filtered air or Cu-UFP aerosols (mass concentration: 196 µg/m3; number concentration: 8.05 × 106 particles/cm3; count median diameter: 38.8 nm; geometric standard deviation: 1.7) via whole-body inhalation for three consecutive days. Bronchoalveolar lavage (BAL) fluid and tissues were collected 24 h post-exposure. BAL samples were analysed for cell counts, viability, lactate dehydrogenase activity, and total protein. Cu tissue burdens were quantified via inductively-coupled plasma mass spectrometry. Cu-UFP exposure caused small but statistically significant elevations in BAL neutrophils and protein content. Cu-exposed mice had elevated Cu in BAL fluid and cell pellets, though Cu concentrations did not differ across most extrapulmonary tissues. APP/PS1 mice showed lower frontal cortex Cu than WT mice, regardless of exposure. Acute Cu-UFP inhalation induced modest lung inflammation and barrier disruption without Cu accumulation in distal tissues, likely reflecting high particle solubility and effective clearance. These findings suggest that reactive metal components of ultrafine PM pollution may contribute to AD risk through inflammatory mechanisms. Supported by R01 AG083020, P30 ES001247, and T32 ES007026.
Enos et al. (Thu,) studied this question.