Project Abstract: Air pollutants such as nanoplastics have been identified to increase risks for neurodegenerative diseases such as Alzheimer’s disease and related dementias (ADRDs). Studies have found that these pollutants can enter the central nervous system (CNS), however how this happens has not been fully characterized. Olfactory sensory neurons (OSNs) are neurons whose cell bodies are found within the nasal epithelium, sending projections though the cribiform plate and onto the olfactory bulbs (OBs) within the CNS. These neurons endogenously sense compounds in the air to transmit information to the CNS and form a potential direct route for nanoplastics to travel from the nose to the brain. The purpose of this proposal is to characterize the nose-to-brain pathway that nanoplastics can be transported into the brain, whether sex, inflammation, age, or known genetic risk factors for cognitive decline and ADRDs (APOE3/4) influence this pathway, and how microglial dynamics change in vitro, after intranasal nanoplastic exposure. The first set of experiments will use advanced histological techniques and confocal microscopy to investigate the cells involved in this pathway and whether sex, age, genotype and inflammation alter the rate of nanoplastic uptake. The second set of experiments will focus on understanding microglial dynamics after intranasal exposure to nanoplastics through 2-photon microscopy and utilizing antibody staining to further investigate microglial dynamics. Age, sex, genotype, and inflammation will be observed to determine their influence on nanoplastic uptake into the CNS.