Alzheimer's disease signatures in the brain transcriptome of Estuarine Dolphins.

Climate warming is one factor increasing the severity of harmful algal blooms (HABs). Innovative exposure models are needed to understand how HABs affect brain health. Here, we examined HAB exposure on the brain transcriptome of dolphins found stranded in Florida's Indian River Lagoon. We report the neurotoxin 2,4-diaminobutyric acid (2,4-DAB) is 2900 times more concentrated in dolphin brains during bloom seasons compared to non-bloom seasons. The same dolphins show 536 differentially expressed genes whose enrichment reveal impairment in GABAergic synapses, basement membrane alteration, and Alzheimer's disease (AD) risk factors that increase with each subsequent season. Dolphins also display concurrent AD-like neuropathological changes and elevated AD gene expression with 2,4-DAB exposure. Our study demonstrates disproportionate seasonal exposure to 2,4-DAB increases AD signatures in the brain transcriptome. As our climate warms, HABs will continue to intensify. Understanding the impact of HAB exposures will help to identify populations at risk for neurological illnesses.