In a Scottish study, the brains of beached dolphins, whales, and porpoises showed the same biomarkers as the brain of a human with Alzheimer’s. What could it teach us?
A Scottish research team collected the corpses of nearly two dozen marine mammals, including long-finned pilot whales, harbor porpoises, and several species of dolphin who had stranded themselves in groups onshore. In the autopsied brains of some of these animals, the researchers spotted something quite surprising: the same patterns of biomarker proteins — beta-amyloid plaques and tau tangles — that one would find in the brain of a human with early-stage Alzheimer’s disease.
As strange as it sounds, it wasn’t a completely original idea. Back in 2017, a study led by clinician scientist Simon Lovestone from the University of Oxford found evidence of amyloid and tau deposits in the brains of striped dolphins. The new study takes things a step further: This is the first time all the hallmarks of Alzheimer’s were shown in multiple species of the odontocetes family.
Animals with Alzheimer’s — and how they’re helping researchers unlock secrets of the disease in humans
More than 99 percent of experimental Alzheimer’s drugs fail in clinical trials. Many of these drugs are developed in mouse models. One big problem is: Mice don’t actually get Alzheimer’s. Researchers need to genetically modify mice brains to produce human amyloid proteins — the hallmarks of human Alzheimer’s. And in this process, there’s a lot that gets lost in translation.
Drug development researchers in the Alzheimer’s space are increasingly aware that the brains of lab mice aren’t a good representation of Alzheimer’s in humans. The outcome is that many treatments that work for mice don’t work for us. To solve this issue, scientists are looking for animals that develop Alzheimer’s spontaneously. After all, we don’t know why 95 percent of total cases in humans occur as they aren’t caused by specific genetic mutations.
At the end of the day, the most promising models for Alzheimer’s are animals who develop it naturally on their own — complete with amyloid plaques, phosphorylated tau tangles, and brain inflammation. Various primates, dogs, and according to a recent study even dolphins could develop the disease.
Chimpanzees may develop a similar condition as they age but though they develop amyloid pathology, non-human primates don’t develop as many tau tangles as humans do. Squirrel monkeys and baboons are promising models as well. Studying dogs with dementia has yielded some interesting possibilities for human interventions. Scientists are even trying to develop miniature human brains where they can replicate the disease.
Dolphins may have another advantage as a disease model: Unlike dogs, chimpanzees, and other primates, dolphins experience menopause and may live well-beyond reproductive age, just like humans. Unlike other wild animals, they may also survive well into the later stages of the disease, because they live in social groups where healthy animals may help the cognitively impaired.
So, what’s the deal with dolphins and dementia?
While previous studies suggested that toxins from bacteria found in algal blooms lead to the development of amyloid pathology in dolphins, scientists weren’t certain if this occurred spontaneously or if tau was involved.
Nonetheless, that finding suggests that exposure to bacterial toxins may trigger the disease, according to Deborah Mash, Ph.D., co-author of a 2019 study showing this link.
“With increasing frequency and duration of cyanobacterial blooms in coastal waters, dolphins might provide early warning of toxic exposures that could impact human health,” Mash told Being Patient.
Following up on Mash’s work, Scottish researchers set out to see if different species of dolphins, whales, and porpoises showed the telltale signs of developing spontaneous forms of Alzheimer’s.
Their study published last month in the European Journal of Neuroscience is the first to document all three hallmarks of the disease in the brains of the marine mammals they studied: amyloid plaques, tau tangles, and brain inflammation.
Studying these changes could provide insight into the causes of Alzheimer’s and provide new avenues for treatment, lead author and veterinary researcher Mark Dagleish said. He added that, even if they don’t experience any cognitive symptoms as a result of this damage, these brain changes suggest that something about their environment, diet, or social ties is serving as a buffer.
“We’ve got the same pattern, the same type of lesions [damage caused by the disease], opening the window for us to look at some of the early mechanisms of Alzheimer’s disease,” Dagleish told Being Patient. “If you can work out the mechanism, then you can hopefully slow down the disease, or stop it.”
Lessons from the deep
Of the 22 beached marine mammals Dagleish’s team studied, they identified three individuals, belonging to three different species, that showed evidence of Alzheimer’s disease.
The study’s results suggest that dolphins, whales, and porpoises do develop the same hallmark signs of Alzheimer’s in their brains that humans do. But changes in the behavior or cognition of these animals still need to be studied to confirm that they do occur alongside the development of amyloid, tau, and inflammation.
Some of the healthy animals stranded themselves alongside a sick animal. According to Dagleish, this suggests they unknowingly followed a “sick” leader into shallow waters.
“We do know that with Alzheimer’s in humans, your spatial awareness goes early on,” he said. “That would be quite critical if you’re leading other animals from memory of where to go.”
Most people die in the last stages of Alzheimer’s, making it almost impossible to study the earliest stages of the disease in humans. The dolphins that get stranded do not get a chance to progress to a further stage of the disease — if researchers get there in time, have the rare chance to autopsy a brain in an early Alzheimer’s state, providing invaluable insight, Dagleish said.
“It gives us a window into the mechanisms causing the development [of Alzheimer’s],” he added, noting that his team will need to look at a lot more dolphins in the future.
With research projects underway to track and identify individual dolphins and whales, as well as record their songs, Dagleish’s team hopes it will be possible to spot some of the symptoms of cognitive decline alive in the wild. Since these animals live in social groups, “they’ll help each other when one is sick,” he speculates, adding that this may allow animals to survive in later stages of the disease.
The researchers also hope to collect more brain samples from stranded animals in the future. Studying trained and captive animals could provide another glimpse into the progression of Alzheimer’s, Dagleish said.
“You could actually test these animals for cognitive deficits,” he suggested, noting that zookeepers and trainers get to know their animals over the course of years, so they can spot when an animal may first develop cognitive problems.
