Alzheimer's, Down Syndrome and Atherosclerosis Share Link
What do Alzheimer's disease, Down syndrome, and atherosclerosis have in common? According to two recent studies, all three of these diseases, and possibly diabetes as well, share the same disease mechanism: protein beta amyloid, which is commonly associated with Alzheimer’s. Therefore, all of these diseases share a common link.
Nearly twenty years ago, Dr. Huntington Potter proposed that Alzheimer’s disease and Down syndrome were the same disease, and few people agreed with him. Today, evidence gathered by Potter and his colleagues at the Florida Alzheimer’s Disease Research Center, University of South Florida Health Byrd Alzheimer’s Institute, points a finger at beta amyloid, which damages the microtubule transport system that moves chromosomes, proteins, and other substances around inside cells. When the microtubule network is damaged, the result can be the development of new cells with the incorrect number of chromosomes and an abnormal assortment of genes.
One disorder associated with Alzheimer’s is Down syndrome: Potter’s previous research has shown that all Alzheimer’s patients have some cells with three copies of chromosome 21 (trisomy 21), rather than the usual two. Trisomy 21 is a characteristic found in people who have Down syndrome. Potter notes that “Alzheimer’s disease probably is caused in part from the continuous development of new trisomy 21 nerve cells, which amplify the disease process by producing extra beta amyloid.” His findings indicate that Alzheimer’s disease could be considered a late onset type of Down syndrome. In addition, by age 30 to 40, all people with Down syndrome develop an accumulation of amyloid protein and other brain pathology seen in Alzheimer’s disease.
Both of the new studies were conducted in mice and human cell cultures that modeled Alzheimer’s disease. The findings from both studies suggest that protecting the microtubule network from amyloid damage may prevent or even reverse Alzheimer’s disease and associated disorders. In the new study published in Molecular Biology of the Cell, Potter and his team now show that the Alzheimer’s-associated amyloid protein disrupts the microtubule transport system, which in turn triggers the chromosome and gene abnormalities.
In the second study, published in PLoS ONE, investigators found another consequence of the damage to the microtubule network by amyloid protein. They focused on the protein’s effects on the metabolism of low-density lipoprotein (LDL) cholesterol, a substance that causes atherosclerosis, cardiovascular disease, and stroke. Many people with Alzheimer’s also develop these diseases, as well as diabetes.
The researchers found that the amyloid damage to the microtubule network also interfered with LDL metabolism, which in turn can allow this bad cholesterol to accumulate in the arteries and block blood flow to the heart and brain. Other key proteins, including insulin receptors and receptors for brain signaling molecules, are also believed to be impacted by amyloid damage to the transport system. “If these receptors are unable to function properly,” notes Dr. Potter, “it may lead to diabetes and problems with learning and memory.”
Approximately 5.3 million people in the United States have Alzheimer’s disease, according to the Alzheimer’s Association, and the number is expected to greatly increase in coming decades. The Johns Hopkins Bloomberg School of Public Health researchers report that worldwide prevalence of the disease will grow to more than 106 million by 2050, about four times the current number. The National Down Syndrome Society reports that the syndrome affects more than 400,000 individuals in the United States.
Dr. Potter noted that researchers are “beginning to understand how conditions like cardiovascular disease and diabetes may manifest some of the same underlying disease processes as Alzheimer’s disease rather than being independent diseases that just happen to develop in the same patient,” including Down syndrome and atherosclerosis. These new findings may eventually help develop ways to prevent and treat these related disorders.
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University of South Florida news release, Jan. 15, 2010
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