Multimethod Detection of Micro- and Nanoplastics in Multiple Brain Regions: Associations with Alzheimer’s Disease and Environmental Exposure Risk

Summary Objective: This study aims to determine whether micro- and nanoplastics (MNPs) accumulate in the human brain, evaluate their relationship with Alzheimer’s disease (AD) pathology, and explore whether environmental disadvantage, measured by the Area Deprivation Index (ADI), is related to variation in cerebral MNP burden. Rationale: MNPs are widespread environmental pollutants with emerging evidence of human tissue accumulation and potential neurotoxicity. Preliminary data show detectable MNPs in the brains of individuals with AD and progressive supranuclear palsy. Social disadvantage may increase exposure to environmental risks, potentially elevating MNP burden and susceptibility to neurodegeneration. Aims: 1. Quantify MNPs in the olfactory bulb (OB) and middle temporal gyrus (MTG) of 140 postmortem human brains (70 with AD pathology, 70 without AD pathology) using five complementary detection methods. 2. Assess associations between cerebral MNP burden and AD pathology, adjusting for age, sex, APOE genotype, postmortem interval (PMI), and other covariates. 3. (Exploratory) Examine the relationship between ADI and cerebral MNP burden, investigating whether MNP burden varies by level of socioeconomic disadvantage. Innovation: This study employs state-of-the-art environmental toxicology methods rarely applied to human brain tissue, integrated with high-resolution neuropathology and life-course social determinants data. It represents the largest and most methodologically rigorous study of cerebral MNPs to date, and the first to directly examine their links to AD and environmental disadvantage. Significance: Findings could identify a novel, modifiable environmental contributor to AD, inform targeted public health interventions, and advance our understanding of how plastic pollution and social disadvantage may shape brain disease. Impact: By bridging environmental science, neuropathology, and social epidemiology, this study could redefine how we think about environmental risks in neurodegeneration. Demonstrating a link between MNP accumulation, AD pathology, and social disadvantage would establish a new line of inquiry with major implications for public health, regulation, and disease prevention. Project Number: 1R21ES038336-01A1 | Fiscal Year: 2026 | NIH Institute/Center: National Institute of Environmental Health Sciences (NIEHS) | Principal Investigator: Diego Mastroeni | Institution: ARIZONA STATE UNIVERSITY-TEMPE CAMPUS, SCOTTSDALE, AZ | Award Amount: $430,625 | Activity Code: R21 | Study Section: Neurotoxicology and Alcohol Study Section[NAL] View on NIH RePORTER: https://reporter.nih.gov/project-details/11387111