December 2, 2004
Researchers are searching for new genes that may be linked to the late-onset form of Alzheimer's disease, by far the most common form of the devastating memory disorder. If found, these new genes may help uncover the underlying causes of an ailment that affects more than four and a half milllion Americans and far more worldwide. The findings may also lead to effective new drugs and therapies against the ailment.
"We feel confident that we may be closing in on new Alzheimer's genes," says study leader Richard Mayeux, M.D., co-director of the Taub Institute for Research on Alzheimer's Disease and the Aging Brain at Columbia University Medical Center in New York. His group is searching for new Alzheimer's-related genes among families living in the Dominican Republic.
Scientists believe that Alzheimer's is caused by some combination of nature (genes), nurture (environmental factors), or both. Researchers have previously identified several mutated forms of genes that result in early-onset Alzheimer's, a rare forms of Alzheimer's that runs in families and often strikes younger adults, some as early as age 35.
The far more common form of Alzheimer's strikes seniors in their late 60s, 70s, and beyond. This late-onset form of Alzheimer's has been conclusively linked to a gene called ApoE4, discovered more than 10 years ago in 1993. Unlike the genes that cause early-onset Alzheimer's, ApoE4 only increases the risk of developing Alzheimer's. Just because you carry the gene doesn't mean you will inevitably come down with Alzheimer's. In addition, people who don't have the gene still get Alzheimer's. The hunt for additional genes that may contribute to the disease is an active area of investigation.
In the current study, investigators examined nearly 500 individuals from 96 Hispanic families, most living in the Dominican Republic. "The reason we chose the Caribbean families," Mayeux explains, "is that the Dominican Republic is a kind of genetic isolate. The people there are more homogeneous than in a place like New York." He and his colleagues found strong evidence for Alzheimer's genes on two chromosomes: chromosome 10, an area that has been linked to Alzheimer's in earlier studies, as well as chromosome 18, a novel area for Alzheimer's gene research. The investigators are pursuing additional studies to identify the specific gene or genes involved.
The hunt for genes that increase the risk of Alzheimer's is important; identifying such genes may answer key questions about how the disease arises. Such basic research can shed new light on mechanisms in the brain that contribute to the illness. 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 towards the search for a cure, visit www.ALZinfo.org.
J H Lee, R Mayeux, D Mayo, et al: "Fine mapping of 10q and 18q for familial Alzheimer's disease in Caribbean Hispanics." Molecular Psychiatry 9, pages 1042 - 1051, November 1, 2004.