ARI SHAPIRO, HOST:
Now a new insight into how the brain may protect itself against one risk of aging. There's evidence that a protein produced naturally by some brain cells may ward off Alzheimer's disease. NPR's Jon Hamilton reports on a study of postmortem brains, which seems to confirm the importance of a molecule that has intrigued some researchers for decades.
JON HAMILTON, BYLINE: The protein is called reelin. It became a scientific celebrity last year, thanks to a Colombian man who should have developed Alzheimer's in middle age but didn't. The man was part of a large family in the area around Medellin that carries a very rare gene variant. Dr. Joseph Arboleda-Velasquez of Harvard Medical School says family members who inherit the gene are virtually certain to develop Alzheimer's.
JOSEPH ARBOLEDA-VELASQUEZ: So they start with cognitive decline in their 40s. Then it develops into full-blown dementia - late 40s or early 50s.
HAMILTON: But this man was in his late 60s and still fine. After he died, scientists found that the man's brain was riddled with amyloid plaques, a hallmark of Alzheimer's. They also found another sign of Alzheimer's, tangled fibers called tau. But Arboleda-Velasquez says, oddly, these tangles were mostly absent in a brain region called the entorhinal cortex.
ARBOLEDA-VELASQUEZ: And that region of the brain seems to be very important because it's a region where Alzheimer's kind of begins, like, a lot of the pathology starts there.
HAMILTON: The researchers studied the man's genome, and they found something that might explain why his brain had been protected. He carried a rare variant of the gene that makes the protein reelin.
LI-HUEI TSAI: So people started to get excited about reelin.
HAMILTON: That's Li-Huei Tsai, a professor at MIT who directs The Picower Institute for Memory and Learning. She and a team had already been studying reelin's role in Alzheimer's. They decided to look at postmortem brains from 48 people. About half had shown symptoms of Alzheimer's. The rest appeared to have normal thinking and memory when they died. But Tsai says a few of these apparently unaffected people had brains that were full of amyloid plaques.
TSAI: We want to know what's so special about those individuals.
HAMILTON: The team did a genetic analysis of the neurons in six different brain regions. They found several differences, including a surprising one in the entorhinal cortex - the same area that was protected in the man from Colombia.
TSAI: And we couldn't believe that the neurons that are most vulnerable to Alzheimer's neurodegeneration - they share one feature, which is they highly express reelin.
HAMILTON: In other words, Alzheimer's appears to kill off the neurons that make reelin, the protein thought to help protect the brain from the disease. And the finding fits well with what scientists learned about the Colombian man whose brain had defied Alzheimer's. He had carried a variant of the reelin gene that seemed to make the protein more potent. Perhaps that offset any reelin deficiency caused by Alzheimer's. Tsai says she and her team are now using artificial intelligence to help find a drug that can replicate what reelin does naturally.
TSAI: So we think that we're onto something very important for Alzheimer disease.
HAMILTON: Arboleda-Velasquez from Harvard says the study, which appears in the journal Nature, is likely to have a big impact.
ARBOLEDA-VELASQUEZ: It confirms the importance of reelin, which I have to say had been overlooked.
HAMILTON: Arboleda-Velasquez, who was born in Colombia, says the reelin story owes a lot to the people around Medellin whose lives have been devastated by a rare genetic variant.
ARBOLEDA-VELASQUEZ: These are just people that agreed to participate in research and get their blood drawn and then donate their brain after death. And they changed the world.
HAMILTON: Perhaps in a way that will eventually prevent early Alzheimer's in their own offspring. Jon Hamilton, NPR News.
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