Superfund Research Program
Metals, Critical Windows of Exposures, Epigenetics, and Late-Life Cognitive Function
Project Leader: Marc G. Weisskopf
Co-Investigators: Felicitas Bidlack (The Forsyth Institute), David C. Christiani, Laura Germine (McLean Hospital), Brian P. Jackson (Dartmouth College), Joseph Mangano (Radiation and Public Health Project)
Grant Number: P42ES030990
Funding Period: 2020-2025
Project Summary (2020-2025)
The researchers are studying the relationship between prenatal and early postnatal exposure to metals and cognitive function and decline in older age. They also are conducting a pilot exploration of whether those exposures and cognitive outcomes are associated with changes in blood-derived extracellular vesicle (EV) micro RNA expression (miRNA), which could represent epigenetic mechanisms underlying associations. They are conducting a cohort study among a subset of participants in the original St. Louis Baby Tooth (SLBT) study who donated their baby teeth in the 1950s and 1960s. Based on their pilot work, the researchers anticipate easily being able to enroll 500 former SLBT participants who have responded to questionnaires and undergone cognitive testing. Prenatal and early postnatal exposure of the 500 to several metals will be assessed by measuring metals in baby tooth enamel (using laser-ablation inductively coupled plasma mass spectrometry). A subset of the participants will provide blood samples from which EVs will be isolated and analyzed for EV miRNA expression levels. The SLBT provides a unique setting that allows the researchers to have individual-level biomarkers of early-life metal exposures in older adults on whom they can conduct cognitive function testing. This study setting allows the researchers to have an unprecedented ability to examine whether early-life exposures are related to late-life cognitive health — a hypothesis suggested from animal research but extremely hard to test in humans without the biomarker of such early exposure that the already collected baby teeth in the SLBT can provide.