An additional genetic influence for Alzheimer's disease has been confirmed in families with a high incidence of the disorder, according to a study published in the August 19 issue of the Journal of the American Medical Association.
The study confirms the existence of an Alzheimer's disease susceptibility gene on chromosome 12. The findings also imply there's at least one other gene associated with a risk or susceptibility to late-onset Alzheimer's disease that has not yet been identified.
The 46 chromosomes normally present in every cell of the human body carry hereditary factors encoded in what's estimated to be between 75,000 to 100,000 unique genes. "Defining the gene associated with a family's susceptibility to Alzheimer's will eventually provide researchers with new and otherwise unattainable insight into how the disease occurs," says lead investigator Professor Peter St. George-Hyslop, director of the Centre for Research in Neurodegenerative Diseases at the University of Toronto."
"Although we don't yet know where the Alzheimer's susceptibility gene is precisely located on chromosome 12, there are a number of genes on this chromosome which might be associated with Alzheimer's disease," says St. George-Hyslop. "Our preliminary studies suggest that it is probably not either of two genes on chromosome 12 that have recently been implicated in Alzheimer's disease."
The researchers collected DNA samples from 53 families with two or more individuals affected by Alzheimer's disease. This involved 173 people with Alzheimer's disease and 146 nondemented relatives. Once the samples were checked and showed the Alzheimer's disease was not due to mutations in the known genes, the investigators then studied the samples for a series of DNA markers located on chromosome 12.
"We were able to show these markers were associated with Alzheimer's disease in a family," said co-principal investigator Dr. Lindsay Farrer, a professor of medicine and chief of the genetics program at Boston University School of Medicine. "The next step will be to study many more families in order to identify the exact region. Once we have narrowed the region to a small DNA segment, we can then focus our attention on the genes contained in this segment."
"This type of research -- first defining genetic risk factors and then defining how these genes cause Alzheimer's disease -- provides a strong basis for attempts to develop treatments and preventions based on a rational understanding of the disease rather than simply trying different drugs to see if they work," explains St. George-Hyslop. "There are many more years of hard work ahead of us."
Unlike genetic diseases such as cystic fibrosis and Huntington's disease in which the presence of the gene for these disorders consistently results in having the disease, Alzheimer's disease is complex and involves multiple factors, much like cardiovascular disease. "It's too early to say whether or not the gene on chromosome 12 can be used to predict a person's susceptibility to the disease," notes Farrer.
Alzheimer's disease is a neurodegenerative disorder that is characterized by pervasive and progressive memory and cognition loss, accompanied by physical changes in the brain such as a loss of neurons, deposits of extracellular amyloid plaque and tangles' of fibres between neurons. Epidemiological and molecular genetic data suggest that although there are likely multiple factors influencing the cause of Alzheimer's, genetic factors play a prominent role in many cases.
The research was supported by grants through the Medical Research Council of Canada, The Canadian Genetic Diseases Network, The Alzheimer Association of Ontario, The Howard Hughes Medical Research Foundation, the EJLB Foundation, Telethon and the National Institutes of Health.