Two teams of European scientists say they have discovered new genetic variants associated with Alzheimer’s disease. The variants account for about 20 percent of the genetic risk of the disease, and may lead to a better understanding of its biology, the scientists say.
One of the teams, led by Julie Williams of Cardiff University in Wales, scanned the genomes of about 19,000 patients, the largest study so far conducted on Alzheimer’s, and turned up two variants that have a statistically significant association with the disease. A second study, led by Philippe Amouyel of the University of Lille in France, also found two variants, one of which is the same as detected by the Cardiff team.
The fact that two studies could agree on at least one gene is an advance. More than 550 genes have been proposed in various small-scale studies as the cause of Alzheimer’s, but all have failed the test of replication by others, Dr. Amouyel said.
The three new variants have been detected by using much larger numbers of patients and by employing the new technique known as a genome-wide association study, in which patients’ DNA is scanned with devices programmed to recognize half a million sites of variation along the genome. The new studies were published Sunday in the journal Nature Genetics.
One of the new variants is in a gene active at synapses, the junctions between brain cells, and the two others help damp down inflammation in the brain. Inflammation is a known feature of Alzheimer’s, but it is often regarded as a consequence of the disease. Dr. Williams said that the detection of the new variants, which undercut the brain’s efforts to restrain inflammation, suggested inflammation might play a primary role.
The gene that has the largest effect in Alzheimer’s is a variant called ApoE4, discovered in 1993 in the laboratory of Allen Roses of Duke University. Dr. Roses said that the three new genes had minor effects compared with the variant site near ApoE4, and that their biological role in the disease was unclear, despite the statistical data pointing to their involvement.