Air pollution, the blood and brain metabolome and their effects on Alzheimer's disease and related dementias

Abstract Exposures to ambient air pollution, especially fine particulate matter (PM2.5), have been associated with increased risks of many chronic illnesses, including Alzheimer’s Disease and related dementias (AD/ADRD). Identification and understanding the role of modifiable risk factors is essential for AD disease prevention.

Despite the observed epidemiological evidence, three central and unsolved questions are 1) what components of PM2.5 (e.g., sulfate, nitrate, ammonium, elemental carbon, organic carbon, metals, etc.) are most neurotoxic, 2) the role of other ubiquitous air pollutants (carbon monoxide (CO), nitrogen dioxide (NO2), and ozone (O3))

which often co-occur with PM2.5, and 3) what biological response occurs in the brain following PM2.5 exposure. A better understanding of the specific exposure components and underlying causal pathways revealing the link between PM2.5 and AD/ADRD will provide valuable insight into disease etiology and pathophysiology and

inform environmental regulation and health policy to reduce disease burden. Although omics applications in environmental health research are still nascent, several studies conducted by our team and others demonstrate that the blood metabolome can be used to sensitively map internal biological perturbations

following exposures to air pollution. The brain and the blood metabolome have also been shown to play an important role in the development of AD/ADRD. However, most previous studies had limited sample sizes (N