March 2, 2005
Scientists in Boston have zeroed in on a gene that appears to increase the risk for developing Alzheimer's disease in old age. Further study is needed to clarify the role of this gene and its possible effects on the brain and memory. But continued research may help to unravel some of the underlying causes of Alzheimer's. It may also hasten development of new drugs and therapies effective against the mind-ravaging illness.
In the current study, doctors studied some 1,439 individuals from 437 different families in which at least two members had come down with Alzheimer's. Study participants were given extensive genetic tests and followed for a period of about ten years. Some study participants developed Alzheimer's during this time and died. Their brain tissue was studied and compared with peers who had died but never developed memory loss and other symptoms of the disease.
Individuals who carried the gene in question were significantly more likely to have developed Alzheimer's disease. The gene, which scientists label with the initials UBQLN1, makes a protein called ubiquilin 1. This protein has unique actions in the brain and if a mutated form of the protein is present, it may contribute to memory loss and other telltale signs of Alzheimer's disease. For example, the protein interacts with two other proteins called presenilin 1 (PS1) and presenilin 2 (PS2). In earlier studies by other researchers, PS1 and PS2 mutations have been linked to a rare form of Alzheimer's that runs in families and strikes at a young age, often when a person is in his or her 30s, 40s or 50s.
The current gene, UBQLN1, appears to increase risk for the far more common form of Alzheimer's that strikes much later in life, typically in a person's 60s, 70s, or later. Earlier studies linked this late-onset form of Alzheimer's to another gene called ApoE4, which did not so much cause Alzheimer's but rather increased one's risk for developing it. This new gene might also increase the risk of developing Alzheimer's, but less so than ApoE4. It also works in unique ways and will likely shed new light on what goes on inside the brain during the course of the disease. Several Alzheimer's genes have already been identified, but scientists believe there are more that play a role in the disease.
Just because people might carry the mutated UBQLN1 gene doesn't mean they will inevitably come down with Alzheimer's. However, they may be more likely to develop memory impairment than someone who doesn't have the gene.
Scientists believe that Alzheimer's results from a complex mix of inborn, genetic factors (nature) and external, environmental influences (nurture). In addition to various genes, non-genetic factors may increase someone's risk of developing Alzheimer's include head trauma at an earlier age, major depression and high cholesterol. Still, the cause of Alzheimer's remains obscure in most cases, and much more research is needed.
The hunt for genes and other factors that increase the risk of Alzheimer's is important. Such basic research may answer key questions about how the disease arises and shed new light on mechanisms in the brain that contribute to the illness. The more genetic risk factors for Alzheimer's that are identified, the more likely it will be possible to predict those people who are at greatest risk. This research may also lead to new drugs and effective treatments targeting brain defects that cause memory loss and Alzheimer's.
The Fisher Center for Alzheimer's Research Foundation is leading the way in basic research into the underlying causes of Alzheimer's disease. For more on how the Fisher Center is working to find a cure, visit the www.ALZinfo.org.
Lars Bertram, M.D., Mikko Hiltunen, Ph.D., Michele Parkinson, B.S., et al: "Family-Based Association between Alzheimer's Disease and Variants in UBQLN1." New England Journal of Medicine, Volume 352, Number 9, March 3, 2005, page 884.
Thomas D. Bird, M.D. "Genetic Factors in Alzheimer's Disease" (editorial). Volume 352, Number 9, March 3, 2005, page 862.