Identify genes associated with neurofibrillary tangles in Alzheimer's Disease

Phoenix, AZ, October 10, 2006--Researchers at the Translational Genomics Research Institute (TGen) have released findings that further define the underlying genes associated with Alzheimer's Disease and neurofibrillary tangles (NFTs), a physical problem found in some brain cells of patients with Alzheimer's Disease. Published in the October issue of the journal, Neurobiology of Aging, TGen's researchers have identified several possible genes that could be linked to NFT formation. Additional validation of these genes may open new opportunities to develop therapeutics to specifically target these genes, one day leading to new and smarter treatments for Alzheimer's patients.
Alzheimer's Disease is an irreversible, progressive disorder in which brain cells (called neurons) deteriorate, resulting in the loss of cognitive functions including memory, judgment and reasoning, movement coordination, and pattern recognition. In advanced stages of the disease, all memory and mental functioning may be lost.

The two most significant physical problems in brain cells affected by Alzheimer's Disease are neuritic plaques and NFTs. NFTs are twisted remnants of a protein that is essential for maintaining proper cell structure and function found inside brain cells. An abnormality in this protein disrupts normal cell activity and is thought to contribute to cell death.

"Understanding what leads to brain cell death at the most fundamental level will surely allow new therapeutic strategies to be developed," said Dr. Dietrich Stephan, Director of TGen's Neurogenomics Division and Deputy Director of Discovery Research.

To identify the underlying causes of brain cell death, TGen researchers analyzed the extent to which genes are turned on or off in these cells that are so strongly affected by Alzheimer's Disease. Researchers screened the genetic profiles of brain cells with NFTs and brain cells without NFTs. Of the nearly 40,000 known genes, 225 were associated with NFT formation and may be related to the early stages of NFT formation.

"After comparing the gene expression profiles, we identified genes that are associated with NFTs. These genes serve as a starting point for uncovering the causes of Alzheimer's Disease pathology," said Dr. Travis Dunckley, lead author of the study and an associate investigator in TGen's Neurogenomics Division. "Once we can figure out the genetic cause, we can then use these genes as potential therapeutic targets, meaning that we may be able to develop drugs to either turn on or turn off the genes responsible for causing Alzheimer"s Disease, ultimately affecting patient outcome in a meaningful way."

The next step in the research process is to demonstrate that these genes directly influence the development or progression of Alzheimer's disease, which could ultimately make them potential candidates for new treatment opportunities.

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About TGen
The Translational Genomics Research Institute (TGen), a non-profit 501(c)(3) organization, is focused on developing earlier diagnostics and smarter treatments. Translational genomics research is a relatively new field employing innovative advances arising from the Human Genome Project and applying them to the development of diagnostics, prognostics and therapies for cancer, neurological disorders, diabetes and other complex diseases. TGen's research is based on personalized medicine and the institute plans to accomplish its goals through robust and disease-focused research.

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