A study published in Alzheimer's & Dementia, The Journal of the Alzheimer's Association, led by researchers at Vanderbilt University Medical Center, investigated the frequency of APOE-ε4 and APOE-ε2 gene variants in "super agers." APOE-ε4 is associated with a higher genetic risk for late-onset Alzheimer's disease (AD), while APOE-ε2 is believed to offer protection.
Super agers are defined as individuals aged 80 or older whose cognitive function is comparable to people 20 to 30 years younger, including memory performance above the average of cognitively normal participants aged 50 to 64. The study encompassed 18,080 participants from eight national aging cohorts, representing various race/ethnicity groups.
Key Findings:
- Super agers were 68% less likely to carry the APOE-ε4 variant compared to individuals with AD dementia in the same 80+ age group.
- Super agers were 19% less likely to carry APOE-ε4 than cognitively normal participants in the same age group.
- Super agers exhibited a higher frequency of the APOE-ε2 variant, being 28% more likely to carry it than cognitively normal controls aged 80+.
- They were 103% more likely to carry APOE-ε2 than participants with AD dementia aged 80 or older.
The study, led by Leslie Gaynor, PhD, and Alaina Durant, BS, represents the largest analysis to date identifying differences in APOE-ε4 allele frequency based on super-ager status and the first to establish a relationship with APOE-ε2 allele frequency. These findings support the utility of the super-ager phenotype in researching mechanisms of resilience to AD. The research was funded in part by grants from the National Institutes of Health.