Three New Genes Found That Increase Alzheimer's Risk

Alzheimer's Risk Gene

Two separate research teams have found three new genes that increase the risk of developing Alzheimer’s disease when they contain certain mutations. The three new genes are CLU, CR1, and PICALM, and they are associated with late-onset Alzheimer’s disease.

Until now, the only gene confirmed to increase the risk of late-onset Alzheimer’s disease has been APOE4 gene variant, with several others found to be associated with early-onset disease. People who have APOE4 are three to eight times more likely to develop Alzheimer’s disease. A University of California Irvine team recently reported (August 2009) that a gene called TOMM40 appears twice as often in people who have Alzheimer’s disease than in people without the disease.

Late-onset Alzheimer’s is much more common than the early-onset type. According to the Alzheimer’s Association, about 95 percent of the estimated 5.2 million people in the United States who have this most common form of dementia have the late-onset variety. Discovery of the three new genes may help scientists eventually develop new treatments for the so-far incurable disease.


Two of the new risk genes for Alzheimer’s, CLU and CR1, appear to be similar to APOE in that they all appear to protect the brain from damage, according to neurologist Julie Williams of Cardiff University in Wales who was on one of the research teams. In a statement noted on the Nature Genetics webpage, Williams noted that “perhaps the changes [mutations] we see in these genes remove this protection or may even turn them into killers.”

A “healthy” CLU gene appears to have a role in transporting amyloid molecules and helping prevent them from deposition in the brain. Amyloid plaque deposits damage the brain and are associated with Alzheimer’s disease. Healthy PICALM genes seem to help maintain healthy connections (synapses) between nerve cells in the brain. Destruction of synapses is also associated with Alzheimer’s disease. Healthy CR1 plays a role in inflammation and may help remove amyloid molecules.

Neuroscientists believe that genes play a significant role—60 to 80 percent—in the risk of developing Alzheimer’s disease. The discovery of these three new genes further supports this belief. Through additional study of these genes, those already discovered, and possibly more, scientists hope they can understand how the variations or mutations in DNA change their function and impact a person’s risk of developing Alzheimer’s. They can then use that knowledge to develop new preventive and treatment approaches.

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Washington Post, September 6, 2009
WebMD September 6, 2009