Humans are the only animals known to develop Alzheimer's disease, an age-related brain disorder that causes impaired cognitive functioning and other behavioural problems. Or at least, that's what we thought. For the first time ever, researchers are claiming to have found signs of the disease in the brains of elderly chimps — a discovery that could yield new insights into the dreaded disorder.
New research published in the science journal Neurobiology of Ageing shows that the very earliest manifestations of Alzheimer's disease can be detected in the brains of elderly chimps, and that our closest living primate relatives seem to have something going on in their brains that's preventing the disease from getting any worse. The eventual discovery of this "something" could lead to the development of new therapeutic interventions to treat Alzheimer's and other neurodegenerative diseases in humans.
Humans, as far as we know, are the only animals that develop severe dementia with age. Yes, other animals exhibit signs of ageing — such as arthritis, tooth and bone wear, and even some mild cognitive decline — but there's nothing as severe as Alzheimer's outside of the human experience. We don't know what it is about our brains, or the mechanisms that drive human ageing, that make us vulnerable, which is why scientists are starting to look at other animals for clues — chimpanzees in particular.
This new study is unique in that the researchers had unprecedented access to a large collection of chimpanzee brain samples dating back to the mid-1990s. The brains were provided by the National Chimpanzee Brain Resource, which has been collecting brains of chimps who have died from natural causes at zoos and research centres.
"Very few studies have investigated Alzheimer's disease pathology in chimpanzees, the species... most genetically related to humans," said Mary Ann Raghanti of Kent State University in a press release. "Brain samples from great apes, particularly aged individuals, are incredibly scarce, so a study of this size is rare."
A tau-positive neuron (shown in black) near amyloid deposits within blood vessels (red) in an aged chimpanzee brain. (Image: Kent State University)
Raghanti and her colleagues studied 20 brains from older chimps ranging in age from 37 to 62, analysing the neocortex and the hippocampus — regions of the brain most susceptible to Alzheimer's in humans. The researchers were on the lookout for a pair of proteins associated with Alzheimer's disease, namely amyloid beta and tau. In healthy brains, amyloid beta breaks down and disappears, but for people with Alzheimer's, this protein refuses to go away, resulting in the formation of plaques between neurons. The presence of these plaques sets another process in motion, whereby another protein, called tau, forms tangles that destabilise brain cells.
Together, the neuronal disruptions caused by these plaques and tangles result in the onset of dementia.
As noted in the new study, this analysis revealed traces of amyloid beta plaques in all 20 chimpanzee brains, and as with humans, the volumes of these plaques increased with age.
"The presence of amyloid and tau pathology in aged chimpanzees indicates these Alzheimer's disease lesions are not specific to the human brain as generally believed," explained study co-author Patrick R. Hof from the Icahn School of Medicine.
Interestingly, traces of amyloid beta were higher in chimp blood vessels than in plaques — that isn't what typically happens in humans. A build-up of amyloid beta deposits in the brain's blood vessels does occur in humans (a condition known as cerebral amyloid angiopathy), but the predominant effect of amyloid beta in our species is the production of excess plaque. "This suggests that amyloid buildup in the brain's blood vessels precedes plaque formation in chimpanzees," noted study co-author Melissa Edler.
Raghanti said it isn't clear if the plaques and tangles found in chimps are producing the same level of cognitive decline as seen in humans. "Our samples had been collected over decades, without any consistent or rigorous cognitive data accompanying them," Raghanti told New Scientist. "So it wasn't possible to say whether the chimps had devastating cognitive loss or not." As a reminder, thus far, there's no behavioural evidence to suggest that chimps suffer significant cognitive declines as they age.
The challenge now will be for scientists to figure out what's happening in human brains that's not happening in chimp brains. Speaking to Nature News, Emory University neurologist Lary Walker said that chimps may have some kind of protective effect going on, and that amyloid beta may folding differently in chimps than in humans. More research will be needed to suss this out.
Which brings up a final point: This discovery, while important, means that chimpanzees have suddenly become more valuable as medical test subjects. Study co-author William D. Hopkins, a professor of neuroscience at Georgia State and an associate research scientist at Emory University's Yerkes National Primate Research Center, said as much in the press release: "Findings like those reported in this paper provide significant evidence of the value and need for continued behavioural, cognitive and neurogenomic work with this important species."
That's certainly one opinion, but Hopkin's remarks run in opposition to current trends. Medical research on chimps and other great apes is on the way out, both in the United States and elsewhere. Thankfully, other options exist. But the inability to experiment on live chimpanzees and other animals doesn't mean that science — and work on Alzheimer's in particular — will suddenly stop.