Rudy Tanzi PhD
Rudy Tanzi PhD Joseph P. and Rose F. Kennedy Professor of Neurology, Harvard Medical School/Massachusetts General Hospital
The Alzheimer's Genome Project takes place right here, literally right here in this lab, and was the brainchild of a collaboration between the Cure Alzheimer's Fund and myself. About five or six years ago we had a discussion. We said, you know, if you think about what we know about Alzheimer's disease, there's a before and there's an after. Before a certain event, we knew nothing about what causes the disease. We could describe it, but we had no idea what caused it. It was the equivalent of going to Gillette Stadium at 6 o'clock on a Sunday after a 1 o'clock Patriots football game and trying to figure out what happened there.
You wouldn't come up with football if you didn't know, if you were Martians coming down from space trying to figure it out. So that's how we were from when Alzheimer described the disease in 1906 to 1986. In 1986, we found the first Alzheimer's gene, and this was a gene that I found as a -- I first found it when I was a student at Harvard, and then two other groups independently found the same gene. This gene told us where the amyloid came from, this toxic sticky substance in the brain. Suddenly we said, "Oh, this isn't just junk that just accumulates from this and that. It's a specific junk that comes from just one big molecule, a protein."
It's funny because when I was a student and I said I was going to go after this gene, you know, some of my mentors and advisors at Harvard Medical School said, "Hey, wait a minute, that senile plaque you see in Alzheimer's -- it's a big dump. It's a big garbage heap. You go after the gene that makes this amyloid, you're probably going to find where one tin can came from in the garbage dump. It's not going to help you." I was a young rebel guy, so I didn't listen, and sure enough, but that gene, it turns out, the first gene that makes the amyloid is still the target for drug discovery today -- the number one target. Then we found three other genes, so by 1995 we had four genes that caused Alzheimer's.
Before those four genes, we knew nothing about the cause. We had no idea how to even think about treating it. So when I talked to the founders of the Cure Alzheimer's Fund, the families, the Morbys, the McCances, the Rappaports, I said, "Look, everything we know about this disease right now came from these four genes. The last one we found was in '95. It's been 10 years. This was back in '05. And we also know that these four genes only account for 30 percent of the genetic puzzle; 70 percent remains unknown. Look at what we've done with the first 30 percent. Imagine what we could do with the remaining 70 percent," thus the Alzheimer's Genome Project.
Everything was perfectly set. There were new gene-hunting technologies using gene chips. The Human Genome Project had provided new databases for how to interpret the human genome. Everything was just right. We had collected, really, hundreds, now thousands, of families with Alzheimer's, where you have multiple members so we could analyze their DNA. So, it was just a perfect storm around '05 when we said it's time to do it, and so we did it, and it's been immensely successful.
The first report that came out of it in '08 -- Time magazine made it a top 10 medical breakthrough of '08, and since then we have 100 new Alzheimer's gene candidates that, right here, we're analyzing that DNA trying to find the variations in that DNA, the mutations that cause the disease. Every new gene gives you a new clue and a new shot on goal in terms of therapy -- and not just here but all around the world.
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