The two largest studies of Alzheimer's disease, an international analysis of genes of more than 50,000 people, have led to the discovery of five new genes that make the disease more likely in the elderly and provide tantalizing clues about what might start Alzheimer’s going and fuel its progress in a person’s brain.
The new genes add to a possible theme: so far genes that increase Alzheimer’s risk in the elderly tend to be involved with cholesterol and with inflammation. They also may be used to transport molecules inside cells.
For years, there have been unproven but persistent hints that cholesterol and inflammation are part of the disease process. People with high cholesterol were more likely to get Alzheimer’s disease. In addition, strokes and head injuries, which make Alzheimer’s more likely, also cause brain inflammation.
And researchers say the studies, to be published Monday in Nature Genetics, are so large and well done that they have little doubt that the genes really do have something important to reveal about the disease process.
“The level of evidence is very, very strong,” said Dr. Michael Boehnke, a professor of biostatistics at the University of Michigan who does similar studies in diabetes and bipolar disease.
But while the new genes are clearly linked to Alzheimer’s, each gene only slightly increases an individual’s risk. For that reason, they will not be used to decide if a person is likely to develop Alzheimer’s.
For instance, the new genes are nowhere near as powerful as a gene discovered in 1995, APOE, a cholesterol metabolism gene that can increase risk by 400 percent if a person inherits one copy and 1,000 percent if a person inherits a copy from each parent. In contrast, each of the new genes increases risk by no more than 10 to 15 percent.