Alzheimer's: a cancer-like mechanism?

Alzheimer's: A cancer-like mechanism?

For several years, Alzheimer's disease has been a much-discussed and somewhat controversial topic among neuroscientists. The progressively debilitating disease is now the fourth--and may soon be the third--leading cause of death in the United States, yet its underlying biology remains largely a mystery.

Because many of the symptoms of Alzheimer's disease resemble those of normal aging, much of the current research effort is aimed at finding biochemical "markers' that are unique to Alzheimer patients. Peter Davies, of the Albert Einstein College of Medicine in New York City, reported last year the first (and still the only) such marker--a protein found in the brain tissue of Alzheimer patients but absent in the normal elderly (SN: 11/22/86, p.327). Researchers still don't know what role the protein plays in the course of the disease, but more information should be forthcoming once its amino acid sequence is determined. That process may be completed in a matter of months, Davies says.

Meanwhile, Davies last week presented some surprising new evidence that the protein in question, called A68, is not entirely unique to Alzheimer patients, but is found in the normal developing fetus and infant. "It appears around 32 weeks of fetal life and disappears by age 2,' Davies says. "This suggests that the protein normally has a function to assist in brain development.'

One intriguing possibility, he says, is that the protein may be involved in the "programmed killing' of brain cells that is characteristic of early brain development. Scientists have long known that during the first years of life the brain makes more neurons that it needs, and that many of these neurons are systematically killed. Davies says A68 distribution in the immature brain is similar to the distribution of cells that are known to die during periods of programmed killing. However, he says, "We don't know if [A68 is] just a marker for cell death-- showing us the cells that are about to die--or if it is something that actually contributes to cell death.'

In any case, he says, the protein's reappearance in adults with Alzheimer's may represent an error in gene regulation similar to that seen in certain cancers. Cancer involves the repeated replication of adult cells as if they were still in their early developmental stages.

"Thinking of Alzheimer's disease as sharing some of the characteristics of cancer is truly a novel idea,' Davies says. However, he adds, such a model is compatible with current scientific knowledge about Alzheimer's disease, including the apparent combination of both genetic influences and unidentified environmental factors that seem to play a role in triggering the disease.

Other explanations for Alzheimer's abound. The "autoimmune school,' for example, has maintained a dedicated following, but the proposition that Alzheimer's is essentially an autoimmune disease continues to stir controversy. Although there is evidence that immune system cells and proteins may be present in the brains of some Alzheimer's patients, such evidence is difficult to interpret: Is the immune reaction the cause or the effect of Alzheimer's disease?

Whatever the answer, the research is stimulating some scientists to question the traditional assumption that the brain is immunologically "privileged,' or anatomically isolated from the body's immune system. Alzheimer researchers are finding increasing evidence of immune components in the brain, including T cells, natural killer cells and human leukocyte antigens. They say this suggests that the blood-brain barrier may not be as impermeable as scientists have assumed, or that the central nervous system may even have its own independent immune arsenal.