Tests Detect Alzheimer’s Early Stages Disease May Be Diagnosed Decade Before Its Effects

For the first time, brain images have captured the insidious destruction of approaching Alzheimer’s disease in people whose thinking and memory are still rich and vigorous.

Combining brain scans with careful genetic screening, doctors can actually see bad spots inside the brain that are the all-but-certain early stages of the devastating illness.

This latest innovation means doctors may be able to diagnose Alzheimer’s more than a decade before it actually starts to steal its victims’ mental powers.

“Accurate and early detection of Alzheimer’s disease has been a goal for many years. This study shows it is possible to do that,” said Zaven Khachaturian, director of the Alzheimer’s Association’s Ronald and Nancy Reagan Research Institute, named for the disease’s most famous recent victim.

Many experts, however, caution against screening for impending Alzheimer’s disease in completely healthy people because no one can predict precisely when the disease will start - or do anything to stop it.

The new technique is part of a whirlwind of research that over the last three years has brought doctors much closer to understanding and perhaps even treating Alzheimer’s disease. All of it stems from the surprise discovery that a gene implicated in heart disease also appears to be involved in most Alzheimer’s cases.

Dr. Eric M. Reiman and colleagues from Good Samaritan Regional Medical Center in Phoenix began with a blood test for the suspect gene and coupled its results with a form of brain imaging called positron-emission tomography - PET for short. They published their results in today’s issue of the New England Journal of Medicine.

The gene is known as apolipoprotein E, or apo E. It comes in three varieties - apo E-2, E-3 and E-4. It turns out that the E-2 version of the gene protects people from getting Alzheimer’s, while E-4 makes it start at a younger age. The risk from E-3, the most common apo E gene, falls in between.

Since each person inherits two copies of every gene, one from each parent, everybody has one of six possible combinations of apo E, and each confers a different risk of Alzheimer’s. However, no combination guarantees development of the disease.

Scientists have determined, however, that people born with two E-3 genes develop Alzheimer’s 15 years later, on average, than people with two E-4s. With a combination of one E-3 and one E-2, the typical onset is later still.

About one-third of Americans carry one E-4 gene, but the worst genetic luck is to inherit two E-4s. These people, who make up 2 percent to 3 percent of the U.S. population, get Alzheimer’s at an average age of 70.

An estimated 4 million Americans have Alzheimer’s, and 100,000 die of its effects every year.

Reiman’s team set out to see if they could find signs of damage in people with the double E-4 genetic susceptibility. They studied 11 men and women, average age 56, who had two E-4 genes and a family history of Alzheimer’s but no symptoms of the disease yet.

Next, they performed PET scans, which look for areas of low metabolic activity inside the brain. When given to Alzheimer’s victims, PET scans show eight specific spots, four on each side, where brain cells are dead or less active.

Deficits in the exact same areas showed up in people with double E-4s, the researchers found, although the low-activity spots were not as broad and intense as in Alzheimer’s patients. By comparison, people who did not carry an E-4 gene had no such clear pattern. There were exceptions, however, and some volunteers without an E-4 gene had brain scans similar to those of people with the gene.

The discovery of the role of apo E opens new strategies to slow or stop the progression of Alzheimer’s. It may be possible to block the bad effects of E-4 or mimic the protection of E-2 with new medicines, for example.

Reiman said by monitoring the brains of genetically susceptible people with PET scans, doctors should be able to tell whether treatment is working without waiting years for symptoms of Alzheimer’s to occur.

“Right now, PET and apo E blood tests should not be used to predict a person’s risk of developing Alzheimer’s,” he cautioned. “They don’t tell us for sure whether they will develop this terrible illness. They don’t tell us when they will develop symptoms, and they don’t tell us what we can do about it.”

Even if dementia starts, there is no foolproof way to tell whether Alzheimer’s is at fault since many conditions can cause similar problems.

Nevertheless, Athena Neurosciences Inc. of South San Francisco, Calif., is developing a simple commercial blood test to reveal apo E genes. It should help doctors make a diagnosis for patients showing possible Alzheimer’s symptoms. The test is expected to cost about $200.

Dr. Allen D. Roses of Duke University, who discovered the link between apo E and Alzheimer’s and has consulted with Athena, plans to present data at a neurology meeting next week showing that people with Alzheimer’s-like dementia almost certainly have the disease if they carry two E-4 genes or one E-4 and one E-3.

Roses said he expects the apo E discoveries to lead to Alzheimer’s drugs that will reach human testing within a decade.

“It could be well before that,” he said. “It will take a certain amount of luck.”