Mad Cow And Alzheimer's Have Surprising Link
Scientists have discovered a surprising link between Alzheimer's disease and mad cow disease. It turns out both diseases involve something called a prion protein.
The finding, which appears in the journal Nature, could explain one of the great mysteries in Alzheimer's disease: How components of the plaques that form in patient's brains are able to damage brain cells. It also could point the way to new treatments for the disease.
"It's very exciting," says Lennart Mucke, director of the Gladstone Institute of Neurological Disease and a professor of neurology and neuroscience at the University of California, San Francisco. "The study shines the light on a very unexpected component."
Mucke was not involved in the study, but wrote an article that accompanied it in Nature.
In mad cow disease, and a similar human condition called new variant Creutzfeldt-Jakob disease, prion proteins fold into an abnormal shape that appears to cause degeneration of the brain and spinal cord. Prion diseases can be transmitted by eating the brain or spinal cord of a sick animal.
In Alzheimer's, prion proteins appear to play a different role, says Stephen Strittmatter, one of the new study's authors and the Vincent Coates Professor of Neurology at Yale University School of Medicine.
Strittmatter says there's no evidence the prion proteins fold into an abnormal shape or actually cause Alzheimer's. Instead, they seem to interact with early stage plaques in the brain in a way that allows those plaques to damage brain cells.
Strittmatter's team made the discovery after looking at hundreds of thousands of molecules that occur naturally in the brain. The prion protein turned out to be the best at interacting with a protein called amyloid-beta, which is what forms the plaques in Alzheimer's
"At first they said, 'No that can't be,'" Strittmatter says. "It's too bizarre that these two diseases would share this common protein."
But he says it seemed less strange when they considered that both diseases affect brain cells and cause dementia.
"Once you start thinking about the details," Strittmatter says, "there are so many shared similarities that it actually begins to make a lot of sense."
After showing that the amyloid-beta from plaque could interact with prion protein, the researchers needed to demonstrate that the combination could harm brain cells.
So the Yale team exposed mouse brain tissue to small clusters of amyloid-beta.
In tissue from normal mice, which contains non-infectious prion proteins, the amyloid interfered with brain cells' ability to communicate.
Then, the team took a slice of tissue from a special mouse whose brain contained no prion protein.
"That slice no longer responded," Strittmatter says. "It carried out completely normal functions."
No prion protein, no problem.
It's still unclear exactly how prion proteins allow amyloid beta to affect brain cells. And the study certainly doesn't suggest that prion proteins cause Alzheimer's.
But Mucke says if prion proteins work the same way in people as in mice, the new research could lead to a drug that would prevent Alzheimer's by keeping prion proteins from interacting with amyloid-beta.
Mucke says finding such a drug could happen relatively quickly because scientists already have spent so many years studying mad cow disease.
"We know a great deal about the biochemistry and biology of prion protein," he says, "which should really facilitate the development of drugs."
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MELISSA BLOCK, host:
This is ALL THINGS CONSIDERED from NPR News. I'm Melissa Block.
MICHELLE NORRIS, host:
And I'm Michelle Norris. Researchers have discovered a surprising link between Alzheimer's disease and mad cow disease. It turns out both involve a strange protein called a prion. NPR's Jon Hamilton reports.
JON HAMILTON: Alzheimer's and mad cow both destroy the brain but in very different ways. Mad cow and a similar disease in people are caused by prions -not the normal prion protein that all brains have, but a deformed infectious prion that creates holes in the brain. Alzheimer occurs as sticky plaques build up around brain cells, but it's been unclear how these plaques interrupt the workings of the brain. They don't seem to affect brain cells directly. Researchers at Yale University thought the answer might be that plaques team up with some other molecule, but they were caught off guard by what they found.
Dr. STEPHEN STRITTMATTER (Professor of Neurology, Yale University): At first, we said, no that can't be it. It's, it's too bizarre that these two diseases would share this common protein.
HAMILTON: Stephen Strittmatter and his team had screened hundreds of thousands of molecules that occur naturally in the brain. Only one was a good match - the prion protein, or as some people say it prion.
Dr. STRITTMATTER: Now that was a real surprise, not what we were expecting at all. And it's really quite striking because there's this whole - separate from Alzheimer's disease - an entire set of diseases called prion diseases that are based on the cellular prion protein.
HAMILTON: But Strittmatter says maybe it isn't so surprising that there's a connection between mad cow and Alzheimer's.
Dr. STRITTMATTER: Once you start thinking about the details, there's so many shared similarities, that it's - actually begins to make a lot of sense.
HAMILTON: For example, both diseases kill brain cells and both cause dementia. The next question was what did prions and plaque working together do to brain tissue? To find out, the Yale team exposed mouse brain tissue to the main substance in Alzheimer's plaques, amyloid peptide. In tissue from normal mice, which contains non-infectious prion protein, the Alzheimer's peptide interfered with the brain cells ability to communicate. Then the team took a slice of tissue from a special mouse, whose brain contains no prion protein.
Dr. STRITTMATTER: That slice no longer responded to the presence of this Alzheimer's peptide. Instead, it carried out completely normal functions whether the A beta-peptide from Alzheimer's was there or not.
HAMILTON: In other words, no prions, no problem. It's still unclear exactly how prions allow the plaque proteins to affect brain cells and the study certainly doesn't suggest that prions themselves cause Alzheimer's. But Lennart Mucke, a brain researcher at the Gladstone Institutes at the University of California San Francisco, says although the finding is only in mice, it could be very exciting.
Dr. LENNART MUCKE (Brain Researcher, Gladstone Institute, University Of California San Francisco): One would want to know whether these disease causing (unintelligible) between amyloid proteins and the prion proteins happen in the human brain.
HAMILTON: And if it does, could a drug prevent Alzheimer's by keeping prions from interacting with amyloid? Mucke says these questions will be easier to answer because scientists have already spent so many years studying mad cow disease.
Dr. MUCKE: We know a great deal about the biochemistry and biology of prion protein, which should really facilitate the development of drugs and specifically at the prion protein.
HAMILTON: The new research appears in the current issue of the journal Nature.
JON Hamilton, NPR News. Transcript provided by NPR, Copyright National Public Radio.
