Brain's Ancient Immune System May Play A Role In Alzheimer's : Shots - Health News Their first epiphanies came during musings over beer, and evolved into a decade of teamwork. Two Harvard researchers explain why they think Alzheimer's disease may be traced to an immunity glitch.

Scientists Explore Ties Between Alzheimer's And Brain's Ancient Immune System

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A new breakthrough may have emerged from research into Alzheimer's disease and it popped up, if you please, during cocktail hour over some beer and Bordeaux. NPR's Jon Hamilton tells us how two scientists found a surprising link between Alzheimer's and an ancient part of the immune system.

JON HAMILTON, BYLINE: Fear has fueled a lot of bad ideas. But in 2007, it led to a good one.

ROB MOIR: The story from my side starts at attitude readjustment hour.

HAMILTON: Rob Moir studies Alzheimer's disease at Harvard Medical School in Massachusetts General Hospital. It was a Friday afternoon, so Moir was sipping a Corona and being a scientist, he was also surfing random scientific papers online.

MOIR: I cruise wherever my fancy takes me.

HAMILTON: On this day, it took him to some ancient molecules that are still present in the immune system.

MOIR: They've been around 500 million years.

HAMILTON: Moir says one thing these ancient molecules do is wrap themselves around any germ they see. This encapsulates the invader until newer parts of the immune system can get mobilized.

MOIR: They're extremely important. They're not like legacies from an immune system we don't use anymore. If you don't have them, you're going to die in a couple of hours.

HAMILTON: As Moir read paper after paper, he realized that one of these ancient molecules was nearly identical to a molecule he sees everyday.

MOIR: It looks just like peas in a pod.

HAMILTON: It's called amyloid. And in people with Alzheimer's, amyloid molecules clumped together to form sticky plaques. So there's striking similarity to a molecule that fights infection was really surprising. Even more surprising on that same Friday afternoon, another Alzheimer's researcher was also drinking Coronas and pondering the immune system.

RUDY TANZI: I was going go over gene data in my office right next to Rob's.

HAMILTON: Rudy Tanzi was reviewing a list of genes he'd found that were somehow related to Alzheimer's.

TANZI: I noticed that many of the genes coming up were involved with innate immunity.

HAMILTON: Innate immunity is the fancy scientific name for the ancient immune system.

TANZI: And I was like, what does that mean? So I wondered into Rob's office carrying my Corona in hand. And I said, what do you know about innate immunity in the brain?

HAMILTON: The scientists decided to team up. Moir says they came up with a plan while sipping wine on the deck of Tanzi's house along the coast.

MOIR: And we spent a lot of evenings out there making a dent in his very nice cellar.

TANZI: Rob, they're going to think we're a couple of lushes. I mean, you know, it was good Bordeaux - much better than the Corona, but...

HAMILTON: The two men began to discuss a wild idea. What if amyloid was a part of the ancient immune system? Would have its purpose was to protect the brain by wrapping up foreign invaders? Moir says they suspected that the brain produced amyloid for the same reason an oyster forms a pearl.

MOIR: May be amyloid plaques are a brain pool and a way for our body to trap and permanently sequester these invading pathogens.

HAMILTON: It was a pretty radical idea. For decades, most scientists thought amyloid was just a toxic waste product.

MOIR: In all those scenarios, it's bad, bad, bad, bad.

HAMILTON: But Moir and Tanzi thought amyloid was usually good, unless the brain made too much. Then, it could kill brain cells and lead to dementia. Tanzi says that idea was not well received by other scientists.

TANZI: I had folks emailing me - ex-mentors, Nobel lawyers saying, Rudy, have you lost your mind?

HAMILTON: So Tanzi and Moir set out to prove that amyloid really was part of the immune system.

TANZI: Luckily, neither Rob nor I really have a good track record of listening to people.

HAMILTON: The effort took years. But in 2010, Moir and Tanzi showed that amyloid was really good at killing germs in a test tube. And in 2016, they showed it did the same thing in worms and mice.

TANZI: It was very clear that amyloid protected against infection. That if a mouse had meningitis or encephalitis - if that mouse was making amyloid, it lived longer.

HAMILTON: Today, lots of scientists are studying the link between the ancient immune system and Alzheimer's. And Tanzi says it's become clear that Alzheimer's involves a lot more than just plaques and tangles in the brain.

TANZI: Even though we really concentrate on these plaques and tangles in Alzheimer's disease, it looks like it's the brain's immune system - the very primitive immune system of the brain that's going awry. And the plaques and tangles are part of that system.

HAMILTON: The question now is what's going wrong? It could be that the ancient immune system is overreacting to viruses or bacteria that get into the brain. Or maybe it's confused and is attacking healthy cells, a lot like what happens in diseases like lupus or multiple sclerosis. Moir says if either of those ideas is right, it may be possible to interrupt the process before it leads to Alzheimer's.

MOIR: That's a pretty good outcome from a couple of Coronas 10 years ago (laughter).

HAMILTON: Jon Hamilton, NPR News.

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