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So far, Alzheimer’s has been unyielding. But research now under way may start answering major questions about when the disease begins and how best to fight it.


A radioactive dye called PIB (for Pittsburgh Compound B) has made it possible to use PET scans to find deposits of amyloid, an Alzheimer’s-related protein, in the brains of live human beings. It may lead to earlier diagnosis, help doctors distinguish Alzheimer’s from other forms of dementia and let them monitor the effects of treatment.


Studies with the dye have already found significant deposits in 20 percent to 25 percent of seemingly normal people over 65, suggesting that they may be on the way to Alzheimer’s, though only time will tell.
Though PIB is experimental now, studies began in November that are intended to lead to government approval for wider use.


Currently, for the most common form of Alzheimer’s disease, which occurs after age 65, there is no proven means of early detection, no definitive genetic test. But PIB tests might be ready before new treatments emerge, making it possible to predict who will develop Alzheimer’s — without being able to help.
Researchers are also using M.R.I. scans to look for early brain changes, and testing blood and spinal fluid for amyloid and other “biomarkers” to see if they can be used to predict Alzheimer’s or find it early.
Studies of families in which multiple members have dementia are helping to sort out the genetic underpinnings of the disease.


Finally, experiments are under way to find out whether drugs and vaccines can remove amyloid from the brain or prevent its buildup, and whether doing so would help patients. The new drugs, unlike the ones now available, have the potential to stop or slow the progress of the disease. At the very least, the drug studies will be the first real test of the leading theory of Alzheimer’s, which blames amyloid for setting off a chain of events that ultimately ruin the brain.


The potential market for prevention and treatment is enormous, and drug companies are eager to exploit it. If a drug could prevent Alzheimer’s or just reduce the risk, as statins like Lipitor do for heart disease, half the population over 55 would probably need to take it, Dr. Thies said.


If new drugs do emerge, they will come from studies in patients who already have symptoms, Dr. Thies said. But he said the emphasis would quickly shift to treating people at risk, before symptoms set in. Many researchers doubt that even the best preventive drugs will be able to heal the brains of people who are already demented.


Dr. John C. Morris, director of the Alzheimer's disease research center at Washington University in St. Louis, is answering readers' questions.


Treating preventively, Dr. Thies said, “will be more satisfying to patients and physicians, and there will be an economic incentive because you’ll wind up treating more people.”
The only thing that could slow the drive for early treatment, he said, would be serious side effects — and Dr. Morris, at Washington University, said drugs powerful enough to treat Alzheimer’s would probably have strong side effects.


Researchers are especially eager to study people with a family history of Alzheimer’s disease because the children of Alzheimer’s patients have a higher-than-average risk of dementia themselves, and tracking their brains and minds may open a window onto the earliest stages of the disease.


Being a research subject may have advantages, according to one person in a study.


“We’re the first ones in line,” she said. “If I am genetically predisposed, and they have a preventive medication, they’ll tell me right away.”


Alzheimer’s Beginnings
Some forgetfullness is normal. Distraction, fatigue and medications can contribute. A joking rule of thumb about Alzheimer’s is actually close to the truth: it’s O.K. to forget where you put your car keys, as long as you remember what a key is for. But worsening forgetfulness is a cause for concern.


Doctors use standard memory and reasoning tests to diagnose dementia, along with symptoms reported by the patient and family members. The term “mild cognitive impairment” is sometimes applied to small but measurable memory problems. But its meaning is unclear: some studies find that the impairment can resolve itself, while others suggest that it always progresses to dementia.


Even if older patients think more slowly or take longer to remember, as long as they can still function independently, they are not demented, Dr. Morris said.


Dr. Morris said, “We think that by the time an individual begins to experience memory loss there is already substantial brain damage in areas critical to memory and learning.”


No one knows whether the disease affects thinking, mood or personality before memory fails. Researchers think that the brain, like other vital organs, has a huge reserve capacity that can, at least for a time, hide the fact that a disease is steadily destroying it.


“I’m speculating that it does affect you throughout life,” said Dr. Richard Mayeux, a professor of neurology, and epidemiology at Columbia University and co-director of its Taub Institute for Research on Alzheimer’s Disease and the Aging Brain. “I think there’s a very long phase where people aren’t themselves.”


He said those findings also made him wonder about the widely dispensed advice to read, take courses, solve puzzles and stay mentally active to ward off Alzheimer’s. The advice is based on studies showing that highly educated people have a lower risk of Alzheimer’s than do less-accomplished ones. But does that mean that mental activity prevents Alzheimer’s — or vice versa?


There were two types of deposits, plaques and tangles. Plaques occur between nerve cells, and are now known to consist of clumps of beta amyloid, an abnormal protein. Tangles form inside nerve cells, and are made of a protein called tau that is normally part of a system of tubules that carry nutrients to feed the cell. Once tau is damaged, the nerve cells essentially starve to death.


It was thought to be different from “senility,” which was assumed to be a consequence of aging. But then researchers compared the brains of younger people who had died of Alzheimer’s with those of elderly people who had been senile, and discovered the same pathology — plaques and tangles. Senility, they decided, was not a natural part of aging; it was a disease.


The Amyloid Hypothesis
The leading theory of Alzheimer’s says that beta amyloid, or A-beta, is the main culprit, building gradually in the brain over decades and short-circuiting synapses, the junctions where nerve cells transmit signals to one other. Gradually, the theory goes, the cells quit working and die.


Everybody produces A-beta, but its purpose is not known. People who develop Alzheimer’s either make too much or cannot get rid of it. Although scientists once blamed plaques for all the trouble, more recent research suggests that the real toxins are smaller bundles of A-beta molecules that form long before plaques do.


Dr. Dennis J. Selkoe, a professor of neurologic diseases at Harvard said that just as lowering cholesterol can prevent heart disease, lowering A-beta may prevent Alzheimer’s or slow it, particularly in the early stages — provided that drugs can be created to do the job.


Several drugs and vaccines are now being tested that either block the production of A-beta or help the body get rid of it.


Researchers are also testing anti-amyloid antibodies which are proteins made by the immune system, as well as blood serum that contains the antibodies.


Eventually, Dr. Selkoe said, screening tests for Alzheimer’s “will be like getting an EKG in the doctor’s office at 45 or 50, and you’ll start treating right away to prevent Alzheimer’s rather than treat it.”
Other researchers are less enthusiastic, noting that there have been numerous failures and disappointments along the way. A vaccine study had to be halted in 2002 because 18 of 300 patients developed encephalitis and 2 died. Some scientists worry that anti-amyloid vaccines in general could be dangerous, in part because the role of amyloid is not well understood and the brain may actually need it.


Many families hope to keep Alzheimer’s patients at home, but not all can manage it, especially if family members have to go work or patients become combative, incontinent, immobile or unable to sleep at night.


This article is excerpted from the New York Times on December 26, 2007.  The full article can be reviewed on line, in their archives.