Determining the effects of life-course exposure to coal-fired power plants on alzheimer's disease and related dementias neuropathology

The National Institute on Aging awarded $107,818 to the University of Wisconsin - Madison on August 10, 2026, under the Aging Research program (CFDA 93.866) to develop geospatial metrics quantifying residential exposure to coal-fired power plant pollution and evaluate associations between life-course exposure dosage and timing to Alzheimer's disease and related dementias neuropathology.

The research addresses gaps in understanding how air pollution from coal-fired power plants—which produce neurotoxic heavy metals including lead, cadmium, and mercury—influences ADRD pathogenesis across critical windows of the life-course. The project will develop a geo-spatial metric defining residential exposure to coal-fired power plant pollution and quantify exposure timing and dosage to identify associations to ADRD neuropathology as a foundation for mechanistic understanding and inform novel therapeutic and policy-based prevention strategies.

The award period runs from August 10, 2026, through August 9, 2027. Work is performed in Madison, Wisconsin. This is a Project Grant, the standard assistance type under the NIA Aging Research program.

Abstract

Proximity to coal-fired power plants (CPP) has been linked to increased mortality and poorer health, but little is known about its effects on alzheimer's disease and related dementias (adrd) or how critical windows of exposures across the life-course may influence adrd pathogenesis. Air pollution is a modifiable environmental exposure linked to the pathogenesis of adrd; however, the fundamental mechanisms linking air pollution to adrd across the life-course are only partially known, motivating the investigation of the environmental-biological relationship to inform novel therapeutic approaches and policy-based strategies for prevention. The long-term objective of this work is to reduce adrd disparities through pollution exposure modification and development of novel therapies. The short-term objectives are to (i) develop a GEO-spatial metric defining residential exposure to CPP pollution and (II) quantify CPP exposure dosage and timing across the life-course evaluating for associations to adrd neuropathology as a first step towards better mechanistic understanding. The overall hypothesis is that earlier and greater exposure to CPP will predict higher risk of adrd neuropathology burden. The rationale supporting this hypothesis is that cpps produce heavy metals (i.e., lead, cadmium, and mercury), which are known neurotoxicants that interact with the biological processes implicated in adrd. Given the long latency period of adrd, there is a significant etiologically relevant period when environmental exposures may impact neurodegeneration; therefore, time-concordant (to calendar year) life-course exposure estimates to CPP heavy metal toxicants are necessary. Lifetime individual-level heavy metal exposure via air pollution from CPP is challenging to measure retrospectively given geospatial resolution and data limitations. Because no direct measure is available, the proposed study links decedent neuropathological samples from a multi-site brain bank cohort to life-course spatial pollution metrics. Area-based measurements of exposure to CPP, rooted in environmental protection agency (EPA) methodology, provide an accepted and validated population-level estimate of exposure. Previously derived residential histories for this multi-site adrc cohort enable the development of life-course exposure estimates. Aim 1: determine the geospatially estimated CPP exposure to heavy-metal toxicants across the life-course for a multi-side adrc cohort of brain donors. Aim 2 (dosage evaluation): determine the impact of cumulative geospatially estimated CPP exposure to heavy-metal toxicants across the life-course on adrd neuropathology, including amyloid and TAU burden. Aim 3 (timing evaluation): determine the impact of geospatially estimated CPP exposure to heavy-metal toxicants during developmental life-course windows on adrd neuropathology. This proposal will advance our understanding of exposure to heavy metals across the life-course and adrd neuropathology, provide me with the skills to establish a new pollution measure that will further my study of the pollution exposome and brain health, and ultimately launch my career as an physician scientist.