Alzheimer's : New Drug Developmen, Risk Factors, Eluding Alzheimer's

by Food and Drug Administration (FDA)

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New Drug Development

New drugs are emerging from the basic science laboratories and moving toward testing in human trials. "The ones furthest along are based on the amyloid hypothesis," says Thies. The hypothesis is that AD starts with the accumulation of amyloid plaques, and that limiting this accumulation will change the progress of AD.

Scientists have isolated enzymes called secretases, which are thought to lead to the formation of beta-amyloid. Secretases are categorized as proteases, the same type of enzymes that are targeted by protease inhibitors to treat AIDS. Drugs called secretase inhibitors are being developed to block beta-amyloid formation, and some of these drugs are now being tested.

Another approach to plaque attack is to stimulate the body's immune system to destroy the beta-amyloid. Scientists developed a vaccine that put amyloid into the blood in the hopes of making antibodies to destroy the plaques. The vaccine was successful in transgenic mice — special mice that were injected with human genes that caused them to develop AD-like plaques. But when tested in a human trial, some people showed inflammation of the brain (encephalitis). Further vaccination was stopped, but study participants continue to be followed. Although this particular vaccine may be disappointing, many scientists believe that the strategy of fighting AD by stimulating the immune system still remains an important potential avenue to slow or prevent the disease.

"We are still searching for the sequence of events where we can intervene and cure the disease without causing harm," says Marcelle Morrison-Bogorad, Ph.D., associate director of the NIA's Neuroscience and Neuropsychology of Aging Program. Morrison-Bogorad notes that scientists may someday be able to inject a substance into the blood to draw amyloid from cerebral spinal fluid and the brain. "This can happen in transgenic mice — we don't know whether it happens in humans yet."

Risk Factors

The two biggest risk factors for getting AD are age and genetics, neither of which is in our control, says Thies. Scientists have identified several genes that play a role in early-onset AD, a rare form of the disease that strikes people as young as in their 30s. For late-onset AD, defined as showing symptoms after age 65, a gene that produces a protein called apolipoprotein E (ApoE) appears to play a role. The gene comes in several forms, or alleles. Having the ApoE4 allele increases the risk for getting AD, according to the NIA.

About 40 percent of people with AD have the ApoE4 allele, but inheriting it doesn't mean a person will definitely get AD. Some people with the gene never get the disease, and some without it do develop AD. Once researchers know more about how genetics affects AD, people could be genetically screened and then treated based on their genetic factors.

Some studies have shown that participating in mentally stimulating activities, such as reading books, doing crossword puzzles, or going to museums, may be associated with a reduced risk of AD. Researchers speculate that repetition might improve certain cognitive skills, making them less susceptible to brain damage.

This "use-it-or-lose-it" theory may have value, but further study is needed, says Morrison-Bogorad. AD may actually cause people to stop doing mentally challenging activities because the disease makes it harder to do them, she says. "It's impossible to tease out the cause and effect in these studies. We can only say it's correlative — not causal." Morrison-Bogorad does encourage mental activity. "It keeps you nimble — whether it helps prevent Alzheimer's, we don't know."

Eluding Alzheimer's

No cure or prevention for Alzheimer's disease exists yet, but experts offer some advice to help prolong mental health:

"The best thing people can do is to try to plan for their later years and try to remain as functional as possible," says William Thies, Ph.D., vice president of medical and scientific affairs at the Alzheimer's Association in Chicago. "And stay connected to the world, because the literature suggests that social isolation is a contributor to unhealthy aging."

Steven Ferris, Ph.D., director of the Alzheimer's Disease Center at the New York University School of Medicine, makes three recommendations:

Stay mentally active. "The more you challenge the brain, the more you'll be able to maintain it," says Ferris. "When you're stimulating the brain, you're growing more interconnections and maybe even growing new neurons. The more brain cells and connections you have, the longer you'll be able to function well, even if you get Alzheimer's."

Stay physically active. Physical exercise improves brain function as well as benefiting the rest of your body.

Have a healthy diet and stay in good physical health. These are essential for maintaining good brain function.

Trey Sunderland, M.D., chief of the Geriatric Psychiatry Branch of the National Institute of Mental Health, encourages people to participate in Alzheimer's research studies so that they learn about the illness and are followed carefully for any incremental change that might occur in their health. "Our volunteers have found that they actually get reassured by being in a study," says Sunderland. "For the most part, we're telling them — in our long-term follow-up studies — that they continue to be normal."

About the Author

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