Alzheimer’s disease (AD) is the most common form of dementia, accounting for 60 to 80 percent of cases, and is the only one of the top 10 causes of death in the US with no way to prevent, cure, or impede its progression. People with a family history of AD are known to have an increased risk for developing the disease, and the Ɛ4 allele of the apolipoprotein E gene is a well-established risk factor.
Recently, genome-wide association studies have identified 19 additional genetic regions that are associated with Alzheimer’s, including the low-frequency variants TREM2 and PLD3. A new study, led by CDHA affiliate Corinne Engelman (population health sciences), examined the two variants in order to determine their effects on cognitive function.
Engelman and her collaborators analyzed participants from the Wisconsin Registry for Alzheimer’s Prevention (WRAP), managed by the Wisconsin Alzheimer’s Institute. The longitudinal study tracks the characteristics and habits of two groups of volunteers. One group is comprised of people with one or two parents with Alzheimer’s. The control is made of individuals whose parents lived to old age without signs of AD or other serious memory problems. The study began in 2001 and now has over 1,500 participants.
The new findings appear in Neurobiology of Aging and support previous results that show an increased risk for Alzheimer’s for people who carry the low-frequency functional variants in TREM2 and PLD3. The research suggests that these variants may be associated with cognitive function, likely due to an AD trajectory—a particularly notable finding for the rare PDL3 variant, which is a less-established risk factor for Alzheimer’s.