A Test for Alzheimer's?

By Joe Levine

The symptoms are dramatic enough: the initial forgetting of small things such as house keys and dates, followed by deepening confusion, hostility and depression. Then the long, slow slide back into childlike dependence, until the victim can no longer sit up, speak or go to the toilet. Yet even then, when family and friends have suffered the heartbreaking deterioration of a loved one, it is still impossible to name the slow killer with absolute certainty. Only after the patient has died and an autopsy is done can the core of the brain be examined for the telltale dead nerve cells and tangled fibers that denote Alzheimer's disease, the senile dementia now recognized as the nation's fourth largest killer.

The cause of Alzheimer's and its cure remain unknown. This week, however, an important breakthrough will be announced in Washington that may change this bleak picture. At the annual meeting of the Society for Neuroscience, scientists from New York City's Albert Einstein College of Medicine will reveal that they have identified what could be the first fully accurate diagnostic indicator of Alzheimer's in living people. The find could lead to improved therapy and even, in the next several years, to an understanding of what causes the illness.

The indicator, identified by Biochemist Peter Davies, 38, and his graduate student Benjamin Wolozin, 28, is an abnormal protein in the brains of & Alzheimer's victims that also appears in the spinal fluid of living patients thought to have the disease. It is not known if the protein, called A-68, plays a role in causing the illness, but so far it is unique to Alzheimer's; that is, it has not been linked to other brain disorders. If further trials prove A-68 a reliable indicator, Davies says, a routine laboratory test for Alzheimer's could be available in a year.

The condition was first identified in 1906, when German Physician Alois Alzheimer autopsied the brain of a woman with classic senile dementia. Because the woman was middle-aged, however, and because senility was considered a natural consequence of aging, Alzheimer's disease went unrecognized among the elderly until the 1960s. Today it is believed that Alzheimer's affects 5% to 10% of people over the age of 65, including half of all nursing- home residents.

In looking for the disease's source, scientists have proposed everything from faulty genes that cause accumulations of damaging proteins to viruses and environmental toxins. As with cancer, all of these factors may be involved; the difficulty lies in knowing where the chain begins. In 1976, for example, Davies observed that the brains of Alzheimer's victims lack certain chemicals that are crucial to memory and cognition; however, he subsequently decided that the deficiency was merely a symptom and embarked on a hunt for a cause.

He focused his search on the crippled central brain tissue where those chemicals normally originate, hoping to find a large accumulation of an abnormal protein that was inflicting the damage. Using monoclonal antibodies, which bind to specific proteins and thus act like biological homing pigeons, the Einstein researchers eventually isolated and identified A-68. Subsequent autopsies, as well as two rare brain biopsies of living Alzheimer's patients, confirmed that A-68 is unique to the disease, and further tests showed it can be found in spinal fluid.

A diagnostic test developed from A-68 could offer several key benefits. First, doctors could weed out the large number of patients currently misdiagnosed with Alzheimer's, people whose symptoms mimic those of the mind- eroding disease. Many of these people are probably suffering from such disorders as stroke, malnutrition or depression, and could be treated. Second, says Davies, the presence of A-68 "appears to be one of the very early pathological effects of Alzheimer's disease" -- meaning the protein could be ; used to diagnose Alzheimer's while the patient's dementia is still reversible. If a cure emerges in the next few years, early diagnosis would save lives.

Finally, A-68 may help cause the disease. Though some medical detectives think Alzheimer's is triggered by a viral gene, Davies believes the disease is at least activated, if not actually caused, by a defective human gene "not normally turned on in the brain" that produces A-68. The search for the gene already centers on chromosome 21, which, when present in triplicate, causes Down's syndrome, a severe form of retardation. Most Down's patients who live past the age of 30 develop neurological signs of what appears to be Alzheimer's. In fact, the disease may also be hereditary, but that is a difficult theory to prove partly because the affliction so often strikes late in life. Carriers of the gene simply may not live long enough to develop symptoms.

The hunt continues elsewhere for the cause of Alzheimer's as well as for a cure. At the University of California at San Diego, for example, Pathologist George Glenner is searching for another protein that could indicate the disease through a simple blood test. For now, though, the spotlight is on Davies. Three drug companies have already approached him about a clinical test for suspected victims. Such inquiries are premature, but Davies clearly is excited about the results of his decade of research. "Alzheimer's is a picture that is beginning to come together," says the researcher, who first took an interest in the brain at age 16 while volunteering for the mentally retarded at a hospital in his native Wales. "In 1974, when I began working on Alzheimer's, it was considered a diffuse degeneration of the brain. Now it's regarded as a very specific neurological disease, and A-68 is a strong new lead to understanding its development."

With reporting by Christine Gorman/New York