April 4, 2011 -- Scientists have discovered five genes linked to an increased risk for late-onset Alzheimer's -- a finding that sheds light on the still mysterious disease and could lead to new predictive tests and treatments.
Two mammoth research teams -- one from the U.S., the other from Europe -- identified variations in the genes ABCA7, MS4A, CD2AP, CD33 and EPHA1 that are associated with an increased susceptibility to the disease. The results were published as two separate reports today in Nature Genetics.
"This is the culmination of years of work on Alzheimer's disease by a large number of scientists, yet it is just the beginning in defining how genes influence memory and intellectual function as we age," Gerard Schellenberg, leader of the University of Pennsylvania study, said in a statement.
The U.S. study, which was carried out by researchers from 44 universities and research institutions across the country, involved genetic analysis of more than 11,800 people with Alzheimer's disease and almost 11,000 elderly people who were "cognitively normal."
The discovery is an important step in a long journey toward new treatments for the neurodegenerative disease that impairs memory and cognition.
"We're all tremendously excited by our progress so far, but much remains to be done, both in understanding the genetics and in defining how these genes influence the disease process," Schellenberg said.
Alzheimer's disease is the leading cause of dementia and the sixth leading cause of death in the U.S., according to the Centers for Disease Control and Prevention. Although specific genetic mutations are known to cause the early onset form of the disease, the late onset form is thought to arise from a complex interaction of susceptibility genes and other risk factors.
"The present reports provide new information that fills in some of the important knowledge gaps in our understanding of the genetics of the common form of late-onset Alzheimer's disease," said Dr. Gary Small, director of the UCLA Center on Aging, who was not involved in the study.
Gene Discovery Could Lead to Tests, Treatments
The first major Alzheimer's disease susceptibility gene -- apolipoprotein E, or APOE -- was reported nearly two decades ago. But it only explained one part of the genetic contribution to a disease marked by several abnormal features, including plaques of a protein called amyloid, tangles of a different protein called tau and inflammation.
"APOE-e4 and the other genes identified earlier are related to the accumulation of amyloid in the brain; these new genes are involved in inflammatory processes, lipid metabolism and the movement of molecules within cells," Dr. Richard Mayeux, a lead scientist for the Alzheimer's Disease Genetics Consortium, which published the American study, and chairman of neurology at Columbia University Medical Center, said in a statement.
Mayeux said the new genes reveal three new pathways involved in the degeneration of neurons in the brain's memory center.
"Therefore, we may now have four pathways that are critically related to the disease and that could really make a difference in how we study and potentially prevent and treat it."
But while new genes may offer new targets for treatments, the trouble may lie in detecting Alzheimer's disease before it's too late.
"The challenge for translating these genes into interventions lies in figuring out how and in whom we can initiate the intervention long before clinical symptoms are evident," said Dr. Samuel Gandy, professor of Alzheimer's disease research at Mount Sinai School of Medicine and past chair of the National Medical and Scientific Advisory Council of the Alzheimer's Association.
Gandy said by the time memory impairment begins, it can be as many as 20 years too late to intervene.
"The new genes are tremendously important, but realistically, they will not provide any time soon any new genetic tests or any new drugs," Gandy said.
Importance of Early Detection
Recently, much Alzheimer's disease research has focused on identifying biomarkers detectable in the blood or on brain scans that signal disease processes long before symptoms set in.
"The field of Alzheimer's disease is moving toward the idea that we need to treat not only people with the symptoms of the disease but also those without any symptoms but at elevated risk," said Zaven S. Khachaturian, president of the the Campaign to Prevent Alzheimer's Disease by 2020.
While the discovery of five new susceptibility genes is exciting, the ultimately challenge is to tease out how out they interact with other factors that confer risk or protection to predict who will get the disease, Khachaturian said.