A team led by researchers at Washington University School of Medicine has identified variations in a gene that doubles a person’s risk of developing Alzheimer’s disease. The research was published online in the journal Nature.
Over the past two decades, scientists have discovered a number of common genetic variants linked to early-onset (which strikes before age 65) and the more common late-onset forms of Alzheimer’s disease. But those variants account for only a fraction of Alzheimer’s cases. The newly identified variations, found in a gene never before linked to Alzheimer’s, occur rarely in the population, making them hard for researchers to identify. But they’re important because individuals who carry these variants are at substantially increased risk of the disease.
As part of the new research, the investigators focused on families with several members who had Alzheimer’s. They sequenced all the protein-coding genes from several individuals in each of 14 families, using whole exome sequencing. Some family members had an Alzheimer’s diagnosis but others did not.
The investigators compared DNA from affected individuals in a family to those in the same family who didn’t have the disorder. Eventually, they identified two families that carried the same variation in the phospholipase-D 3 gene (PLD3). The variation was present in affected family members but not in the elderly family members who did not have Alzheimer’s disease. “This PLD3 variant, like the recently identified rare variant in the TREM2 gene, appears to confer more risk for Alzheimer’s disease than other genes identified by the latest genome-wide association studies,” says lead author Carlos Cruchaga, PhD. Read the study abstract.
