The study, which examined close to 75,000 people in 15 countries, doubles the number of known genes that increase Alzheimer’s risk in the elderly. “The international group identified as many new genes in this one study as have been found over the last 15 years combined,” says one of the study’s senior authors, Richard Mayeux, MD, chair of neurology at Columbia University Medical Center.
The study, which is being published in the Nov. issue of Nature Genetics, was conducted by dozens of researchers through the International Genomics of Alzheimer’s Project (IGAP), created in 2011.
None of the 11 new genes has as strong an effect on Alzheimer’s as the APOE4 gene, which was linked to the disease in the 1990s. APOE4 accounts for about 20 percent of cases, while the strongest of the new genes accounts for, at most, 8 percent of cases.
The significance of the discovery lies instead in the number of possible new drug targets revealed by the study, including some that are involved in processes never before considered in Alzheimer’s.
“Six of our new genes suggest the existence of new pathways underlying Alzheimer’s,” Mayeux says. These areas include the junction between neurons in the hippocampus, the area of the brain where Alzheimer’s begins, and the activity of other cells in the brain surrounding the neurons.
Other new genes uncovered by the group are related to processes in the brain that are well-known contributors to Alzheimer’s, including the processes that lead to the build-up of toxic amyloid beta and tau deposits, or help confirm newer ideas such as inflammation. The identification of new genes involved in these processes may ultimately lead to new drugs.
What’s most needed now, the investigators say, is an intense effort to understand the precise roles of all 22 genes in the development of Alzheimer’s disease.
“At the end of the day, we want to find a way to halt or prevent the disease,” Mayeux says. “The prospects of doing this are now somewhat greater, but we still have a lot of work to do.”