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Scientists can't get their minds around Alzheimer's

They still aren't sure what causes the disease or how to cure it. And the stakes have never been higher.

December 27, 2007|By Terry McDermott | Los Angeles Times Staff Writer

Here's an example. So far, the primary genetic contribution to normal, or late-onset, Alzheimer's, the most common form of the disease, occurs with the mutation of a gene that makes a protein called ApoE. It might be possible to devise a way to render that protein inactive. But that causes other, potentially larger, problems. ApoE is a lipid transporter. Its main job is to carry lipids, including cholesterol, from the interior of cells to be broken down, destroyed and carried away for disposal. Think of it as taking out the garbage. A drug to attack ApoE would destroy one of the body's natural systems of disposing of cholesterol.

Alzheimer's has been particularly intractable, but there are optimists. Dennis Selkoe of Harvard University, one of the most prominent Alzheimer's researchers, thinks there might be an effective therapy found within the next year or two. He thinks the disease process is now sufficiently understood. "If drugs fail, it will be because they are not potent enough," he said, not because they don't attack the disease process.

Buckholtz, of the National Institute on Aging, said the wide variety of proposals now in circulation reflected the vigor of the underlying science. "The therapeutics are targeted at different pathways that may be involved. I think that's a good thing," he said. "Although it's frustrating they haven't been more efficacious, I continue to be optimistic that by having all these targets available we'll have something soon."

More common are sentiments such as that expressed by Eli Lilly's Karran in the talk he gave to open the San Francisco conference. After describing his notion of what the Alzheimer's disease process was, he said: "If the pharmaceutical industry had known what this looked like, we never would have started working on it."

terry.mcdermott@latimes.com

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