Apes don’t develop Alzheimer’s—at least, not like we do. Although we share a hefty amount of our DNA with our closest primate relatives, humans are uniquely at risk of developing the disease that can erode our sense of who we are.
When I make the diagnosis in my neurology clinic, I tell patients and family members that in most cases, doctors can’t point to a single, definitive cause of the illness. Age, genetics, health, lifestyle factors, and environmental triggers all play a role. But a growing body of research offers another dimension: We can lose our sense of self precisely because our species evolved to have one. In recent years, scientists have been comparing the brains of humans with those of other, closely related species, and teasing out how the genetics, structure, and molecular mechanisms differ. What they’re finding is that the same characteristics that support our unparalleled cognitive abilities make us susceptible to Alzheimer’s disease.
Certainly, the biological hallmarks of Alzheimer’s look different inside the human brain than in the brains of other species. Melissa Edler, a comparative neurobiologist at Kent State University, and her team have identified distinct patterns in how humans and chimpanzees accumulate amyloid plaques and tau tangles, the toxic proteins that build up in brains with Alzheimer’s. She believes that looking at multiple species is going to be crucial to understanding how this disease develops. If nonhuman primates aren’t developing Alzheimer’s, “why aren’t they?” she asked, when we spoke about her work. “What’s different about their brains?”
One answer dates back to the early 2000s, when the Swedish geneticist Svante Pääbo (who went on to win the Nobel Prize for sequencing the Neanderthal genome) wondered what might account for the profound behavioral differences between humans and other apes—after all, we build civilizations while nonhuman primates cannot, without assistance, start a fire. Pääbo and his team of international researchers collected brain, blood, and liver tissue from humans, chimpanzees, orangutans, and macaques. But instead of comparing the genes themselves, they measured the genes’ activity—effectively, how hard each gene was working to make messenger RNA, which carries instructions from DNA on how to make proteins. Gene activity in the liver and blood, they found, was roughly equivalent across the species they tested. But activity in the human brain had ramped up.
Pääbo hadn’t set out to study Alzheimer’s specifically, but his findings hinted at a link between evolution and brain disease that others have pursued more directly. In a study published in 2020, for instance, Thomas Arendt, a neuroscientist at Leipzig University, and his team looked at autopsied brain samples from people with and without Alzheimer’s disease and found nearly 300 genes whose level of activity was different in the Alzheimer’s brains. When they looked at those particular genes more closely, they found that their genetic sequences had undergone a lot of change in a short amount of time—an indication that those genes played an important role in the human brain’s rapid and distinctive evolution. “In other words,” Arendt told me recently, “Alzheimer’s disease is based on changes in the genome that are typically human.”
Other researchers, too, have gathered evidence that supports the idea that evolution and Alzheimer’s are integrally related. A group at Duke University discovered that human evolution had influenced genes involved in the production of amyloid—the main protein that forms Alzheimer’s plaques. Scientists in China and the United Kingdom found that stretches of regulatory DNA that quickly morphed as the brain was evolving are associated with Alzheimer’s risk. Researchers from the MD Anderson Cancer Center, based in Houston, found uniquely human genes that get in the way of a protein called REST, which may guard against Alzheimer’s when working properly. Other studies have presented findings along similar lines. Collectively, these results only add to Arendt’s argument—that the genetic changes that made the human brain may be the same ones that left it imperiled.
The cognitive leap that set us apart also required the human brain to grow. The parietal lobes, which rise toward the crown of the head before sloping down the rear of the brain, are conspicuously larger in humans than in nonhuman primates, as Emiliano Bruner, a senior researcher in hominid paleoneurology at the Museo Nacional de Ciencias Naturales in Madrid, has demonstrated. A structure called the precuneus, tucked along the inner wall of those lobes, is larger too. The parietal lobes help the brain stitch sight, sound, and touch together into a cohesive model of the external world. They also play a central role in our advanced, abstract cognition, allowing for self-awareness, autobiographical memory, and our sense of being the same person across time.
Bruner had been mapping out these areas when he was contacted by Heidi Jacobs, now an associate professor of radiology at Massachusetts General Hospital and Harvard Medical School, who had been studying the same anatomy. For decades, Alzheimer’s research had focused almost exclusively on a different area of the brain—the temporal lobes, its de facto memory hubs. But Jacobs’s work suggested that the parietal lobes were also implicated in the disease’s earliest stages. Bruner and Jacobs began discussing whether the enlargement of these regions could have increased their vulnerability. Soon, they came up with a theory: The parts of the brain that had expanded most dramatically during human evolution were also among the first to be assailed by Alzheimer’s.
This was no coincidence, they argued. The precuneus consumes enormous amounts of energy and generates heat that has to be carefully dissipated to keep the brain functioning at its best. It also sits in a zone where the brain’s blood supply is thinnest, which makes it vulnerable to certain conditions, some of them age-related, that impact blood flow. Myelin, the fatty coating that is crucial for fast signaling between neurons, is also particularly fragile in this area. Essentially, Bruner and Jacobs reasoned, because of the rapid and imperfect reorganization that the parietal lobes underwent during human evolution, the region doing much of the brain’s hardest cognitive work has some of the most precarious infrastructure.
“It is like putting the engine of a Ferrari into a Fiat 500,” Bruner said. “That small car will go really fast, but it’s going to get hot. And braking will be an issue.”
What Bruner calls “braking,” the Yale neuroscientist Amy Arnsten calls “regulation”—specifically, calcium regulation, which supports learning and memory. The failure of that system, Arnsten argues, may be tied to how Alzheimer’s begins.
Most neurons fire because something in the outside world activates them: a flash of light, a sound. Neurons in our most recently evolved brain regions, which help us hold an idea in our minds, or conjure a detailed plan, keep firing even after the initial stimulus is gone. Although competing theories exist, Arnsten and others consider this persistent firing to be the cellular foundation of working memory. These “delay cells” depend on calcium to keep them active, but as we age and the cells’ system falters, calcium can rise to harmful levels, triggering a chain reaction that can cause tau proteins to clump. Over time, those clumps can contribute to the tangles of fibers that are seen in patients with Alzheimer’s.
Arnsten has shown that this apparatus, as well as the damage it causes when it breaks down, increases in lockstep with hominid evolution. Marmosets have the least of it. Macaques more. Chimpanzees, more still. Humans, by far, the most. “The closer to human,” Arnsten said, “the more the Alzheimer’s pathology.”
Our bodies are no strangers to evolutionary trade-offs. Homo sapiens’ vertical spine leaves us vulnerable to herniated discs; our pelvis, narrowed by bipedalism, makes childbirth difficult. We manage these compromises as best we can. But if an evolutionary give-and-take implicates our organ of thought and reason, accepting the compromise is harder.
The suggestion that neurological fragility is the price of a highly evolved mind is not novel, the historian Michael Hagner, who’s studied our understanding of the brain as the locus of personhood, told me. In the 19th century, some physicians and social theorists believed that the overwhelming demands of modern life were overtaxing the nervous system. That inclination, to interpret our cognitive vulnerabilities as the price of progress, has persisted even as more specific diagnoses have emerged to explain our brains’ instabilities.
Therapeutic options for Alzheimer’s remain both scarce and disputed, and understanding the disease’s ties to our brain’s evolution could open new avenues toward prevention and treatment. Amy Arnsten and her colleagues, for instance, are currently developing drugs that target calcium dysregulation, aiming to intervene before the system begins to break down. For now, the notion that human cognition and Alzheimer’s susceptibility share an evolutionary origin remains theoretical, and every time I deliver an Alzheimer’s diagnosis, I am acutely aware that I can offer little to change my patient’s fate. But if losing the sense of self is uniquely human, so is the ability to consider what having one allows us to gain.