In Vitro Neurotoxicity Analysis for Mapping Alzheimer's Disease Risk Due to Particulate Matter Exposure

Yuezhi (August) Li, Joseph V. Puthussery, KEYAO SONG, Jessica Restivo, John Cirrito, Rajan K. Chakrabarty, Washington University in St. Louis

     Abstract Number: 543
     Working Group: Health-Related Aerosols

Abstract
Dementia, encompassing various neurodegenerative disorders, affects over 55 million individuals worldwide, with over 10 million new cases reported annually. Among all these disorders, Alzheimer’s disease (AD) is the leading cause of dementia. Recent epidemiological and animal studies have provided increasing evidence for a potential causal link between exposure to particulate matters (PM) and AD development, highlighting the necessity to elucidate the underlying mechanisms of this association.

This study aims to investigate how air pollutants induce AD by establishing a Neurotoxicity Index (NTI) that gauges the impacts of different PM_2.5 constituents on neural health. We selected various major PM components, including organic matter, sulfate, nitrate, ammonium, black carbon (BC), dust, and transition metals, that are representative of emissions from urban, agricultural, and natural sources. By exposing the neuron-like Neuro 2a (N2a) cells to these pollutants, we first examined their influence on N2a cell viability. The cells were exposed to a concentration gradient of each PM component for 24 hours to determine the lethal concentration of 50% cell death (LC₅₀). The PM components have a wide range of LC₅₀ values. For example, copper oxide (CuO), a common pollutant from vehicular braking, shows an LC₅₀ of 2.5 µg/mL, whereas BC from incomplete combustions has an LC₅₀ of 120 µg/mL. Notably, copper sulfate, which is water-soluble, exhibits a much higher LC₅₀ of 58 µg/mL than the insoluble CuO. This indicates that the subsets of the same PM component can have different neurotoxicity and may affect the neurons via different mechanisms. Following cell viability, we will continue to examine the influence of air pollutants on other crucial neurotoxicity indicators such as mitochondrial function, reactive oxygen species generation, and amyloid β plaque formation. The complete NTI will be instrumental in translating cellular-level changes into actionable health risk data.