Possible approach to treating Alzheimer's Disease

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The disease, which progessively damages memory and cognitive functioning, typically occurs when cells in the brain overproduce a protein called amyloid-B, or beta amyloid, and create a damaging plaque material. To stop the development of Alzheimer's disease, scientists must create a medication that inhibits beta amyloid production, increases cells' ability to rid the brain of that protein, or both. That is, they have to turn off the faucet and open one or two chemical "drains" to solve the problem. Stopping beta amyloid over-production cannot be the only potential solution, he said.

"That only represents about 5 percent of all Alzheimer's cases," he said. "And we know that in most cases, the 'faucet' is not turned up. That leads to the other possibility which is that one or more 'drains' are clogged. So you get the same effect but for a different reason." Leissring, two other Scripps Florida scientists, and three Florida Atlantic University undergraduates are performing research on this type of dementia.

For many years, much of Alzheimer's research focused on stopping beta amyloid production. Now, with the University of Chicago/Argonne National Laboratory discovery, scientists are working to activate IDE. The Scripps Florida team is focusing on that approach.

Leissring has studied this angle with his former Brigham and Women's Hospital colleague Dennis Selkoe, a leader in Alzheimer's disease research. The two scientists reviewed and wrote commentary about the Shen and company breakthrough for the online edition of the journal Nature. "Selkoe could win the Nobel Prize for his Alzheimer's research," Leissring said.

"Our group was the first to show that if you increase the drainage system by increasing the amount of these proteases that degrade beta amyloid, we could completely prevent Alzheimer's disease inside an animal model," Leissring said. Proteases start and stop enzymatic activity by cutting the molecular link between amino acids. Scripps scientists are aided by a $10 million Kalypsys research robot that can quickly screen thousands of chemical compounds a day for potential drug uses. Scripps is the only academic facility with such a device, he said. The institution, however, needs more funds to keep its laboratories running. "I was over budget the day I walked into the lab. Currently government funding is at record lows. It's just tragic because there are so many new opportunities that have emerged in the last five to 10 years. We really should be accelerating," he said.