The Effect of Microplastics Exposure on Alzheimer’s Disease Pathology Characterized using APP/PSEN1 Mice

Alzheimer’s disease and related dementias (AD/ADRD) are one of the most prevalent cognitive disorders, affecting more than 6 million Americans over the age of 65. While the exact cause of AD and ADRD is still unknown, several risk factors have been identified, including exposure to environmental toxins. In recent years, nano- and microplastics (NMPs), defined as particles ≤ 1 µm and ≤ 5 mm in size, respectively, have emerged as pervasive environmental pollutants. Previous studies have shown NMPs are able to accumulate in peripheral tissues throughout the body of both humans and mice, raising concerns regarding their potential health impacts. Furthermore, NMPs have been demonstrated to cross the blood-brain barrier to accumulate through the brain, resulting in alterations in cognitive behavior and immune markers consistent with neurological disease. We recently demonstrated that polystyrene (PS)-NMPs exposure in transgenic mice carrying the APOE4 variant, the largest known risk-factor for developing AD, resulted in marked sex-dependent alterations in locomotion and recognition memory, as well as changes to astrocytic and microglial markers in the brain. Building on these results, we are now examining the effects of NMPs exposure in a mouse model of Alzheimer’s disease pathology (APP/PSEN1). Specifically, this study aims to determine whether chronic exposure to 0.1 µm and 2 µm polystyrene NMPs influences the onset and/or progression of amyloid-beta plaque deposition, alters neuroimmune markers, and affects cognitive function. Preliminary results indicate that chronic exposure to PS-NMPs in APP/PSEN1 mice worsens cognitive impairments, while plaque accumulation was observed to increase taking into account the plaque variability of the family line. Ongoing analyses are also investigating the histological, biochemical, and immunological changes resulting from PS-NMPs exposure.