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Researchers at Mount Sinai School of Medicine are concentrating on a protein known as COX2, which they have shown rises steeply in the brains of patients in the very early stages of the disease. Cells produce COX2 in response to injury, observes Mount Sinai molecular psychiatrist Giulio Pasinetti, who believes it may be COX2--and not beta amyloid--that induces the inflammatory response characteristic of the disease. Anti-inflammatories, in other words, could shortly emerge not only as components of the therapeutic arsenal but also as agents of prevention.
Selkoe is hoping that APOE4 and other as yet undiscovered susceptibility genes will produce clues that point to other potential compounds. For as he notes, Alzheimer's disease, no less than heart disease and diabetes, will almost certainly be found to have multiple causes. For example, the genes implicated so far in early-onset Alzheimer's all lead to an overproduction of beta amyloid. But the genes involved in the bulk of cases, Selkoe strongly suspects, are more likely to do with faulty clearance mechanisms that aren't doing a good enough job flushing out the plaques. A sink can overflow, he observes, for two reasons--if the faucet is too wide and the drain too narrow.
Scientists are struggling to identify environmental factors that may help protect those who carry susceptibility genes like APOE4. It's clear that these genes in and of themselves are not enough to cause Alzheimer's. Like aging itself, they are risk factors, which means that lifestyle choices may prove to be equally important. A number of researchers, for example, believe that elevated cholesterol may contribute not only to heart disease but to Alzheimer's disease as well. Researchers at New York University's Nathan Kline Institute put transgenic mice on high-fat diets, then observed an increase in the rate at which beta amyloid built up in their brains. When they gave the mice a drug that brought cholesterol down, the rate of accumulation slowed.
Cholesterol-lowering drugs, nerve-growth factors, antioxidants, estrogen replacement in postmenopausal women--the verdict on the capacity of such substances to protect against Alzheimer's is not yet in, but it is coming. What is so exciting about the presentations scientists will be making at the World Alzheimer Congress this week is the staggering breadth of research they represent. In coming years, Baptists and Tauists alike will undoubtedly encounter setbacks, and the 10 years that the optimists estimate it will take to get on top of this disease could easily stretch into 20 or 30.
For aging baby boomers, that prospect looms as both bitter and sweet. While a sea change in the treatment of Alzheimer's may not occur in time for their parents, it almost certainly will for them.
--Reported by Alice Park/New York