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Looking for Links Between Genes and Alzheimer’s

Posted By alz01 On November 23, 2010 @ 2:56 am In | No Comments

Researchers are continuing to uncover various genes that may play a role in the onset of Alzheimer’s disease. The findings offer new clues about who will get Alzheimer’s in old age, and why, and may offer new approaches to treating or preventing the mind-ravaging illness.

Scientists at the University of Miami Miller School of Medicine found that a gene on chromosome 6, called MTHFD1L, appeared to nearly double a person’s risk of developing late-onset Alzheimer’s, the most common form of dementia. The findings were published in the journal PLoS Genetics.

"We are hopeful our identification of MTHFD1L as a risk gene for Alzheimer's disease will help us to better understand how this disease develops and potentially serve as a marker for people who may be at increased risk," said Adam Naj, Ph.D., a co-author of the study.

"Identifying this gene is important because the gene is known to be involved in influencing the body's levels of homocysteine, and high levels of homocysteine are a strong risk factor for late-onset Alzheimer's disease," said Dr. Margaret Pericak-Vance, who led the study. Homocysteine is an amino acid that circulates in the blood, and high levels are associated with blood vessel diseases and an increased risk of heart disease and strokes.

The findings provide further evidence of the link between heart health and brain health. "Variations of the MTHFD1L gene have been reported to possibly increase the risk of coronary artery disease,” Dr. Pericak-Vance said. “Since the function of blood vessels in the brain may affect Alzheimer's disease, this finding may also help us understand how homocysteine levels and blood vessel function in the brain affect Alzheimer's disease."

Scientists have identified genes that play a role in the rare, early-onset form of Alzheimer’s that runs in families and which can strike people as young as their 30s or 40s. But the far more common late-onset form of the disease, which becomes increasingly prevalent in old age, is not as well understood.

Studies have shown that having a parent with Alzheimer’s increases your risk of developing the disease. Twin studies likewise suggest that genetic factors play a role in late-onset Alzheimer’s. But until recently, only one gene – called APOE, for apolipoprotein E – was shown to strongly influence risk. Having a form of the APOE gene known as APOE-E4 increases your risk, and about 40 percent of those with Alzheimer’s have the gene. But many people who carry the gene never get Alzheimer’s.

Several other genes are also suspected of playing a role, though the risks they impart is smaller than the risk associated with APOE-E4. Dozens of additional genes are under investigation as possible contributing factors to Alzheimer’s disease, and as yet undiscovered genes may impart different levels of risk as well.

In a separate study in the U.K., researchers at Oxford University found that carrying the APOE-E4 gene may produce changes in the brains of young, healthy individuals who have no memory problems. The investigators studied men and women in their 20s and 30s, and compared them with those over 50.

Scans revealed that the brains of the younger people who had the APOE-E4 gene were normal in size. But they did find some abnormalities in the connections between cells in the white matter part of the brain, suggesting that the gene may have some effects on brain function decades before the memory loss of Alzheimer’s appears. They are conducting follow-up studies to learn more about how genes affect the brain and contribute to Alzheimer’s disease. The findings are consistent with ongoing research into the ways in which genes and brain changes interact to influence Alzheimer’s risk.

Researchers hope that continued study of genes that may contribute to Alzheimer’s will lead to better understanding of the disease. It may also allow for the development of new drugs that may be able to halt or reverse the memory and behavior problems of the disease.

Researchers are only now beginning to understand the complexities of Alzheimer’s. In addition to genetic factors, lifestyle factors like diet and exercise, mental and social stimulation, advancing age, and other environmental components may all play a role in its onset. It will likely take years of continued research to understand the roles of genes and other factors in the development of Alzheimer’s.

By ALZinfo.org [1], The Alzheimer's Information Site. Reviewed by William J. Netzer [2], Ph.D., Fisher Center for Alzheimer's Research Foundation at The Rockefeller University.

Source: PLoS Genetics, Sept. 23. BBC News.


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[2] Reviewed by William J. Netzer: http://www.alzinfo.org/netzer

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