Alzheimer’s and Down syndrome: a genetic link?
Alzheimer’s and Down syndrome: A genetic link? At first glance, no two diseases could seem more dissimilar. Alzheimer’s disease afflicts the elderly; Down syndrome afflicts the unborn fetus. Alzheimer’s affects the brain and central nervous system, and causes slow mental deterioration; Down syndrome affects the chromosomes, causing lifelong mental as well as physical disabilities. Yet despite these differences, “there is very possibly a genetic thread that runs between these two illnesses,” according to Melvyn J. Ball, director of the Neuropathology Research Laboratory at the University of Western Ontario.
The precise composition of that thread is not yet fully understood, but the link between the two diseases is unmistakable. With recent advances in medical treatment, four out of every five of all Down syndrome (DS) adults now reach the age of 50, compared with an average life expectancy of 9 years in 1910. And virtually all of those who live beyond the age of 35 develop physiological signs similar to those of Alzheimer’s disease. “Their brains have the same pathology,” says Charles Epstein, chief of medical genetics at the University of California, San Francisco.
“If we can discover the similarities in the causes of these two diseases, we could learn more about who is vulnerable to Alzheimer’s,” Ball says. DS occurs when an infant is born with an extra duplicated chromosome on the 21st chromosome pair. The cause of Alzheimer’s disease, which afflicts more than two million in the United States, remains unknown.
The link between Down syndrome and Alzheimer’s disease has eluded scientists thus far largely because not all DS adults show outward signs of memory loss–the most outstanding characteristic of Alzheimer’s disease. But most neurobiologists now agree that about 25 percent of all DS adults who survive through their 30s exhibit clear clinical signs of Alzheimer-type dementia before they die, Epstein says. Regardless of the observed clinical evidence, the remaining 75 percent will show pathological evidence of Alzheimer’s–brain-cell lesions, nerve-fiber “tangles” and nerve-cell loss–if their brains are autopsied after death.
The question of genetics, DS and Alzheimer’s is still very much open to speculation. Epstein cites a recent report from Johns Hopkins University suggesting that the development of Alzheimer’s, independent of DS, is hereditary. A second survey, this one in Minnesota, studied several large families whose incidence of Alzheimer’s was far greater than the national average. These families also tended to have a higher frequency of Down syndrome than average, indicating that both Alzheimer’s and DS might indeed “run in the family.”
Epstein cautions that such findings are preliminary, however, and do not seem to hold up in general. “It may have been true in those pedigrees, but not necessarily in other pedigrees,” Epstein says. The only proven link, then, is that these two diseases, one of which is known to be genetic, cause strikingly similar changes in the brain.
Until scientists can isolate the few genes on the extra chromosome that are responsible for the wide variety of abnormalities associated with DS, the precise genetic relationship with Alzheimer’s will remain unresolved. For now, understanding the recently discovered similarities between the two diseases should help to reveal much about how each disease operates and perhaps, ultimately, how to prevent both.
Epstein, Ball and others presented their findings on Down syndrome and Alzheimer’s disease last fall at a conference in New York sponsored by the National Down Syndrome Society.
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