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Spinal Tap May Help Alzheimer's Diagnosis

Proteins in fluid may predict which memory loss will become dementia

MONDAY, Nov. 18, 2002 (HealthDayNews) -- Two proteins present in brain and spinal fluid of people with mild memory trouble may flag those destined to develop Alzheimer's disease.

The proteins, called tau and beta-amyloid 42, are elevated and suppressed, respectively, in the cerebrospinal fluid of people whose wobbly cognition turns out to be the initial stages of Alzheimer's, German scientists have found. Although the degenerative disease has no cure, early treatment can help delay its progression by six months or so. Scientists, therefore, are eager to uncover harbingers of the dementia before it becomes full-blown.

The latest findings appear this month in the Archives of Neurology.

Alzheimer's disease, which is thought to be caused by a buildup of toxic beta-amyloid in the brain, affects an estimated 4 million Americans. The number of patients is expected to quadruple over the next 50 years as the population ages.

A handful of scientists believe that draining cerebrospinal fluid may stall the advance of Alzheimer's by shunting away harmful proteins from the brain. That approach is still experimental and hasn't been proven to work, experts said.

The latest work, led by researchers at the Technische Universitat in Munich, followed 28 men and women with mild cognitive impairment, or MCI. These people have some recall problems but do fine on cognitive tests, can perform tasks of daily living, and don't have dementia.

Over an 18-month period, a dozen of the volunteers went on to develop dementia, 10 with likely Alzheimer's disease. Of the rest, 16 were still considered to have mild impairment, although six had gotten worse and 10 had remained stable.

Patients who ended up with dementia were about six years older, on average, than those whose MCI didn't get that bad.

Those whose MCI worsened, or who developed dementia, had higher than normal tau for their age, the researchers found. Yet levels of the protein weren't elevated in people whose MCI remained steady throughout the study. For beta-amyloid, the finding was reversed, with lower than expected concentrations of the protein in their cerebrospinal fluid.

Researchers found another predictor that didn't require a spinal tap to detect. People who had trouble remembering words on a standard test at the start of the study were more likely to see their memory problems worsen, or turn, into dementia, 18 months later.

Dr. Roger Rosenberg, a brain specialist at the University of Texas Southwestern Medical Center and the editor of the Archives of Neurology, said the findings imply that progressive mild cognitive impairment "is indeed pre-Alzheimer's, rather than a separate disease." What's more, the two wayward proteins appear to act as markers of the condition.

In those with dementia, levels of these proteins typically diverge from normal in the 60s, Rosenberg said. But the bad chemistry of Alzheimer's is probably present at least a decade before its symptoms arrive.

Dr. Gerald Silverberg, a Stanford University neurologist, said the German research "fits with what everyone would expect."

Tau is released by brain cells that are killed by protein plaques and tangles and the inflammation that characterizes Alzheimer's, so higher concentrations of the molecule in cerebrospinal fluid are the echoes of dying neurons. The reason beta-amyloid levels drop in the fluid, Silverberg said, is because more of the substance stays in the brain to do damage.

Silverberg is now leading a small study to see whether removing tau and beta-amyloid from brain and spinal fluid can slow the progression of Alzheimer's disease. Preliminary evidence suggests that cognitive test scores stabilized in the group undergoing the treatment while levels of the two proteins fell, he said. Longer follow-up is needed to see whether the therapy is safe and effective.

In an unrelated study also published this month in the journal, Maryland researchers found that the average 65-year-old with Alzheimer's lives about eight years after the diagnosis is made, while those diagnosed at 90 survive only three years with the disease. The study found that people are typically diagnosed with Alzheimer's 2.8 years after first showing symptoms of the brain ailment.

What To Do

For more on the degenerative brain disorder, try the Alzheimer's Association. You can also try the University of California at Irvine.

SOURCES: Roger Rosenberg, M.D., professor of neurology, University of Texas Southwestern Medical Center, Dallas; Gerald Silverberg, M.D., professor of neurosurgery, Stanford University School of Medicine, Palo Alto, Calif.; November 2002 Archives of Neurology
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