Dolphins exposed to Florida algal blooms show gene changes linked to Alzheimer’s disease

Dolphins living along Florida’s coast appear to be affected by the same types of environmental factors that are being investigated for their potential role in human neurodegenerative diseases. A study published in Communications Biology provides evidence that repeated seasonal exposure to algal bloom toxins is associated with molecular and cellular changes in dolphin brains that mirror some features of Alzheimer’s disease. The findings raise concerns about the long-term effects of harmful algal blooms on marine wildlife and possibly on human health in areas where such blooms are common.

Harmful algal blooms, also called HABs, occur when colonies of algae grow out of control, often fueled by warm water temperatures and nutrient pollution. These blooms release toxins that can accumulate through the food chain, affecting both aquatic animals and land mammals. Acute effects of these toxins are well documented, but their long-term impact on brain health is less well understood.

The Indian River Lagoon, a large estuary stretching along Florida’s east coast, has experienced recurring algal blooms over the last two decades. As climate change warms the region, these events are occurring more frequently and lasting longer.

Dolphins that inhabit the lagoon are long-lived, apex predators. Because they share similar exposure risks with humans and display age-related brain changes, they serve as a valuable species for studying the possible neurological consequences of environmental toxin exposure.

Dolphins have been shown to develop some of the same brain abnormalities seen in people with Alzheimer’s disease, including accumulations of amyloid-beta plaques and tau tangles. The co-occurrence of these markers and the dolphins’ repeated exposure to algal bloom toxins offered a unique opportunity to study how environmental changes may affect brain biology over time.

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“In this study, we aimed to determine if seasonal change can have an impact on brain health. We focused on harmful algal bloom season, since these blooms can produce a number of neurotoxins. We hypothesized that exposure to neurotoxins would be higher during bloom seasons and neurotoxicity would parallel seasonal change,” explained study author David A. Davis, a research associate professor and associate director of the Brain Endowment Bank at the University of Miami Miller School of Medicine.

The research team analyzed brain tissue from 20 bottlenose dolphins that had stranded and died in the Indian River Lagoon area between 2010 and 2019. The dolphins were divided into two groups based on when they died: bloom season (June through November) and non-bloom season (December through May). The researchers aimed to determine whether the timing of death, which served as a proxy for toxin exposure, was associated with measurable changes in the brain.

To measure toxin levels, the team used a highly sensitive mass spectrometry method to detect the presence of 2,4-diaminobutyric acid (2,4-DAB), a neurotoxin produced by algae. They found that 2,4-DAB was present in all dolphin brains but was almost 3,000 times more concentrated in those that died during bloom season.

Next, the researchers examined changes in gene expression across the brain. They used RNA sequencing to map which genes were turned on or off in the cerebral cortex. The dolphins that died during bloom season showed altered expression in more than 500 genes, including many involved in nervous system function and immune response. Several of these genes have also been linked to Alzheimer’s disease in humans.

In addition to transcriptomic changes, the team performed immunohistochemical analysis on brain sections from a subset of the dolphins. These tests revealed deposits of amyloid-beta and phosphorylated tau proteins, which are considered hallmarks of Alzheimer’s pathology. These changes were found in dolphins from both seasons, but the data suggest that the factors associated with bloom season, including higher 2,4-DAB concentrations, may interact with and worsen this underlying pathology.

The study provides evidence that seasonal exposure to 2,4-DAB is linked to biological processes that resemble those seen in Alzheimer’s disease. Specifically, dolphins exposed during bloom seasons showed altered signaling in GABA-producing neurons and changes in genes involved in the brain’s basement membrane, both of which play a role in maintaining brain function and structure.

“Our study shows a direct relationship between seasonal change, toxin exposure and brain health,” Davis told PsyPost. “This study is a clue to the Alzheimer’s disease exposome which is believed to consist of multiple types of exposures throughout the lifespan that contribute to the development of the disease.”

One of the most consistent findings was a seasonal increase in the expression of the APOE gene, a well-known genetic risk factor for Alzheimer’s. APOE was upregulated in dolphins from the bloom season, which is characterized by high 2,4-DAB exposure, and this increase tended to rise with each successive bloom season.

“The most surprising observations were the temporal increase in Alzheimer’s disease risk factor genes with each sequential bloom season,” Davis said.

Other Alzheimer’s-related genes, such as APP and MAPT, were also elevated during bloom seasons, and their expression correlated with the concentration of 2,4-DAB in the brain.

In addition, dolphins exposed to more bloom seasons showed increased expression of genes linked to inflammation and cell death. Several of these genes, including TNFRSF25 and CIRBP, are also involved in human neurodegenerative diseases and stress responses.

As with all research, there are limitations. The study relied on opportunistic samples collected from stranded dolphins, which means the causes of death were not controlled by the researchers. While the dolphins selected had similar age, sex, and health profiles, other unknown factors may have contributed to their deaths or the observed brain changes.

The sample size was relatively small, in part due to the challenge of obtaining high-quality brain tissue from wild marine mammals. Despite this, the researchers applied rigorous standards for RNA integrity and used multiple validation techniques to strengthen the reliability of the data.

Importantly, while the study found gene expression changes that match those seen in human Alzheimer’s cases, it did not assess cognitive function in the dolphins. The presence of Alzheimer’s-like markers suggests a similarity in biological response, but it does not confirm that dolphins experience dementia in the same way humans do.

The findings point to the need for more detailed investigations into how 2,4-DAB affects brain cells over time, and whether this toxin interacts with other environmental or genetic risk factors. Future studies could also explore the prevalence of these changes in dolphins that have not stranded, using non-lethal sampling methods, or in controlled laboratory models.

“We plan to investigate the 2,4-DAB toxin that was detected in the dolphin brain in more detail to investigate its role in triggering neurodegeneration,” Davis said.

Because dolphins are considered sentinel species, their health can provide early warning signs of environmental risks that may also affect humans. Given that South Florida has one of the highest rates of Alzheimer’s disease in the United States, the findings suggest a need to explore whether chronic exposure to algal bloom toxins contributes to regional patterns in human neurodegenerative diseases.

“Our study highlights the relationship between environment and brain health,” Davis concluded. “South Florida had the highest prevalence of Alzheimer’s disease in 2024. Our study focused on dolphins found beached in Florida. The data here could provide a link between increased prevalence of the disease in certain geographics.”

The study, “Alzheimer’s disease signatures in the brain transcriptome of estuarine dolphins,” was authored by Wendy Noke Durden, Megan K. Stolen, Susanna P. Garamszegi, Sandra Anne Banack, Daniel J. Brzostowicki, Regina T. Vontell, Larry E. Brand, Paul Alan Cox, and David A. Davis.