Monday, November 3, 2008

Breakthrough Mapping of Alzheimer's Genome Helps ID Four New Suspect Genes


In 1994 I worked on the start up financing for Myriad Genetics. Revolutionary at the time, Myriad was in the process of acquiring a patent on the breast cancer gene (BRCA) and developing a commercial blood test for predisposition to breast cancer. Since 1994 my sister was diagnosed with breast cancer and my mother with Alzheimer's disease. I know first hand that the identification of gene's that predispose individuals to disease could very well make a difference between life, death, and the quality of life. It should come as no surprise that I am interested in the "Alzheimer's Genome Project".

The discovery of Alzheimer's genes is likely to lead to therapies that could slow, stop, or even cure the disease. This science is a very different approach from those we are more familiar with--clinical trials of drugs. The drugs currently available address the symptoms of the disease once it presents and is identified. Identification of genes that predispose Alzheimer's would allow you to know that you have a probability of contracting the disease--high, low, none--and allow you to do something about the situation.

With breast cancer disease it is easy to understand the importance of knowing if you are predisposed to cancer. Once you know you could take action or you could get more frequent mammograms. Currently there is no cure or therapy for Alzheimer's. However, my own personal experience tells me that there are things that can be done to slow down the disease. I know this from my experience with my mother and I have written about that often on this blog.

Gene testing for predisposition to disease is controversial. Do you want to know or would you rather not know? The good news with Alzheimer's is that once these genes are discovered, mapped, and valid tests are developed you get to make the choice. In my opinion that is a good thing.

Breakthrough Mapping of Alzheimer's Genome Helps ID Four New Suspect Genes

Four novel genes that may significantly increase the risk of the most common form of late-onset Alzheimer's have been identified by researchers at Massachusetts General Hospital and Harvard Medical School, as reported in the November 7th issue of American Journal of Human Genetics. The findings, part of a larger "Alzheimer's Genome Project" (AGP) established three years ago to identify the full set of Alzheimer's disease genetic risk factors, may lead to more aggressive therapeutic interventions to slow, stop or even reverse the effects of the disease. These new therapies would differ from current treatments that only address the symptoms of the disease.

Dr. Rudolph Tanzi, chairman of the Cure Alzheimer's Fund Research Consortium and the Joseph P. and Rose F. Kennedy Professor of Neurology at Harvard Medical School, completed the largest family-based genome-wide association screen conducted to date. More than 400 families affected by Alzheimer's disease were screened to determine genetic variants associated with the inheritance of Alzheimer's. The four genes discovered in the family study are described in the article.
Technological advances are improving the understanding of the genetic mechanism that governs Alzheimer's disease and are making it feasible to identify the complete set of genes influencing risk for Alzheimer's disease, Dr. Tanzi said.
In addition to the genome-wide association screen, Dr. Tanzi and Dr. Lars Bertram of Harvard Medical School have been analyzing Alzheimer's genetics literature to determine which of the hundreds of proposed Alzheimer's candidate genes are genuine disease genetic risk factors. These summarized findings, implicating 30 gene candidates, are updated regularly at http://AlzGene.org (a public Web site sponsored by the Cure Alzheimer's Fund). Tanzi and Bertram highlighted 10 of the most interesting of these genes in the current issue of Nature Reviews Neuroscience. Ultimately, the goal is to combine the results of the Alzheimer's family-based genome-wide association screen with the bioinformatics results of AlzGene.org.
The combined efforts of the family-based genome-wide association screen and AlzGene.org studies have led to the identification of 70 genes containing variants that either confer risk for, or protect against, Alzheimer's, making up the most comprehensive genetic map of the disease.

"This project is the most complete and comprehensive search for the genes that cause Alzheimer's disease published to date," Tanzi said. "Our hope is to use this new information to not only better diagnose and someday predict risk for Alzheimer's but to also learn from these genes the biological causes of Alzheimer's. The knowledge gained from understanding the Alzheimer's-associated defects in these genes will almost certainly accelerate the development of novel therapeutics and hopefully lead to a potential cure for this devastating disease."

The current understanding of the causes and pathological progression of Alzheimer's disease have been made possible by studies of four Alzheimer's genes discovered between 1987 and 1995, three of which were co-discovered by Tanzi. Since these genes account for only 30 percent of the genetic basis of Alzheimer's disease, three years ago Cure Alzheimer's Fund initiated the Alzheimer's Genome Project aimed at determining the remaining 70 percent of the genetic basis of Alzheimer's disease. Taking advantage of major technological and analytical breakthroughs in human genetic studies, the project was able to reach this milestone with a limited budget, led by a contribution of $3 million from Cure Alzheimer's Fund.
"We are on the cusp of a rare 'science moment' that could alter the way we diagnose, treat and prevent Alzheimer's disease," said Tanzi. "Ultimately, the combined results of the family-based genome-wide screen and AlzGene.org will allow for the reliable prediction of Alzheimer's disease while also guiding the development of therapies."

Alzheimer's disease is the most common cause of dementia in the elderly and a burgeoning unmet medical need that only will worsen as individuals continue to live longer. The Alzheimer's Association estimates that as many as 5.2 million Americans are living with Alzheimer's disease, including between 200,000 and 500,000 people under age 65 with young-onset Alzheimer's disease or other dementias. Experts predict that, by 2010, nearly a half million new cases of Alzheimer's disease will occur each year; and by 2050, nearly a million new cases will occur annually.
Cure Alzheimer's Fund has no endowment and passes funds raised directly to selected research as determined by the Cure Alzheimer's Research Consortium. The Foundation has no financial or intellectual property interest in the research funded, and will make known the results of all funded research as soon as possible. At a time when the federal government investment for Alzheimer's research and education is decreasing, Cure Alzheimer's Fund has raised more than $10 million, investing all of it directly into research.

Cure Alzheimer's Fund(TM) is a 501c3 public charity established to fund targeted research with the highest probability of slowing, stopping or reversing Alzheimer's disease. For more information, please visit http://www.curealzfund.org.

Contact: David Roscow
+1-703-276-2772 x21
SOURCE Cure Alzheimer's Fund
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Bob DeMarco is an Alzheimer's caregiver and editor of the Alzheimer's Reading Room. The Alzheimer's Reading Room is the number one website on the Internet for advice and insight into Alzheimer's disease. Bob taught at the University of Georgia, was an executive at Bear Stearns, the CEO of IP Group, and is a mentor. He has written more than 700 articles with more than 18,000 links on the Internet. Bob resides in Delray Beach, FL.

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