"I think we're onto something important for Alzheimer's," MIT neuroscientist Li-Huei Tsai tells NPR, after her team's latest research backs up a pair of previous studies regarding a protein they say may help fend off cognitive decline. That protein, reelin, appears to act as a "protective factor" that keeps a person's thinking and memory intact as the brain gets older—a link that Tsai and her colleagues looked at in a study in September of last year, as well as in a new one published Wednesday in the journal Nature. Their research comes on the heels of research published in May 2023 in which a Colombian man who carries the rare Paisa gene variant was expected to almost certainly develop symptoms of Alzheimer's by middle age, as most of his family members did.
However, this particular man didn't start to see cognitive decline until he was well into his 60s, with no dementia diagnosis until his 70s. When he died at the age of 74, an autopsy revealed that he also had a rare variant of a gene that produces reelin, which is believed to reduce tangles of tau, a neuron-impairing protein that's typically found in the brains of Alzheimer's patients. This particular patient did have tau tangles in his brain, but not in the entorhinal cortex, which controls memory and is usually one of the first parts of the brain to be affected by Alzheimer's, Harvard's Dr. Joseph Arboleda-Velasquez tells NPR.
The September research by Tsai's team examined the brains of more than 425 people and found that those who showed higher cognitive functioning as they advanced in years typically boasted more of a neuron that makes reelin. In their most recent study, a genetic analysis of patients who'd exhibited no signs of Alzheimer's before dying, but whose brains were chockfull of amyloid plaques—another marker of the disease—showed that the neurons in their entorhinal cortexes had one thing in common.
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"They highly express reelin," Tsai tells NPR. Study co-author Leyla Akay adds, per an MIT release: "We can think of reelin as having maybe some kind of protective or beneficial effect. But we don't yet know what it does or how it could confer resilience." Arboleda-Velasquez, meanwhile, praises the Colombian family involved in the initial study for their contributions. "These people agreed to participate in research, get their blood drawn, and donate their [brains] after death," he tells NPR. "And they changed the world." (More Alzheimer's disease stories.)
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