A study of 48 postmortem brains found that a protein appears to protect brain cells from Alzheimer’s disease – even in people with large amounts of amyloid plaques in their brains.
Ari Shapiro, host:
We now have new insights into how the brain protects itself from the risks of aging. There is evidence that proteins naturally produced by certain brain cells may protect against Alzheimer’s disease. NPR’s Jon Hamilton reports on a study of postmortem brains that appears to confirm the importance of a molecule that has intrigued some researchers for decades.
JOE HAMILTON, BYLINE: The protein is called reelin. Last year it became a celebrity in the scientific community, thanks to a Colombian man who should have developed Alzheimer’s disease in middle age, but didn’t. The man was a member of a large family from the area around Medellín who carried a very rare genetic mutation. Dr. Joseph Arboleda-Velasquez of Harvard Medical School said family members who inherit the gene will almost certainly develop Alzheimer’s disease.
JOSEPH ARBOLEDA-VELASQUEZ: So they start to have cognitive decline in their 40s. Then, in the late 40s or early 50s, it progresses to full-blown dementia.
HAMILTON: But this guy is in his 60s and still in good health. After his death, scientists discovered that the man’s brain was riddled with amyloid plaques, a hallmark of Alzheimer’s disease. They also discovered another sign of Alzheimer’s disease, tangled fibers of a protein called tau. But strangely, Arboleda-Velasquez said, most of these tangles are not found in a region of the brain called the entorhinal cortex.
ARBOLEDA-VELASQUEZ: This area of the brain seems to be very important because that’s where Alzheimer’s starts, like a lot of pathologies start there.
HAMILTON: Researchers looked at the man’s genome, and they found something that might explain why his brain was protected. He carries a rare genetic variant that causes proteins to curl up.
LI-HUEI TSAI: So people started getting excited about reelin.
HAMILTON: This is Lihui Tsai, professor at MIT and director of the Picower Institute for Memory and Learning. She and a team are already studying reelin’s role in Alzheimer’s disease. They decided to look at the brains of 48 people after they died. About half develop symptoms of Alzheimer’s disease. The rest seemed to have normal thoughts and memories after death. But some of those apparently unaffected had brains full of amyloid plaques, Cai said.
Tsai: We want to know what’s so special about these people.
HAMILTON: The research team performed a genetic analysis of 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 men from Colombia.
TSAI: We couldn’t believe it, but the neurons that are most vulnerable to neurodegeneration in Alzheimer’s disease—they all have a common characteristic, which is that they highly express reelin.
HAMILTON: In other words, Alzheimer’s appears to kill the neurons that produce reelin, a protein thought to help protect the brain from the disease. The findings fit closely with what scientists know about a Colombian man whose brain was unable to fight off Alzheimer’s disease. He carried a variant of the reelin gene that seemed to make the protein more effective. Perhaps this could counteract reelin deficiencies caused by Alzheimer’s disease. Tsai said she and her team are now using artificial intelligence to help find a drug that could replicate reelin’s natural effects.
Tsai: So we think we’re looking at something really important for Alzheimer’s disease.
HAMILTON: Harvard’s Arboleda-Velasquez says the study, published in the journal Nature, could have a big impact.
ARBOLEDA-VELASQUEZ: It confirms the importance of reelin, which I have to say has been overlooked.
HAMILTON: Arboleda-Velasquez, who was born in Colombia, says the story of the scrolls owes a lot to the people around Medellín whose lives were devastated by a rare genetic mutation.
ARBOLEDA-VELASQUEZ: These are people who just agreed to participate in the study and have their blood drawn and then donate their brains after they die. They changed the world.
HAMILTON: Maybe in a way that ultimately prevents their own offspring from getting early Alzheimer’s. Jon Hamilton, NPR News.
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