The genetic variant most strongly linked to an increased risk of developing late-onset Alzheimer’s disease (AD) is known as APOE-ε4. Another form of the same gene, APOE-ε2, is believed to offer a protective effect, helping to lower the likelihood of developing the condition.
A large-scale study published on 16 January in Alzheimer’s & Dementia, the journal of the Alzheimer’s Association, explored how frequently these two gene variants appear in so-called super agers. These are individuals aged 80 or older whose cognitive abilities remain comparable to those of people 20 to 30 years younger. The research was led by scientists at Vanderbilt University Medical Center and focused on understanding whether genetic factors might contribute to this remarkable resilience.
The findings showed that super agers were 68 per cent less likely to carry the high-risk APOE-ε4 variant compared with people of the same age group who had Alzheimer’s dementia. This alone suggested a significant genetic advantage among those who maintain strong mental function well into later life.
Perhaps even more striking was the comparison with cognitively healthy adults aged 80 and over. Super agers were still 19 per cent less likely to possess APOE-ε4 than their normally ageing peers, indicating that their genetic profile may be uniquely protective, even among those who have avoided dementia.
The researchers also discovered for the first time that super agers were more likely to carry the beneficial APOE-ε2 variant. They were 28 per cent more likely to have this protective gene compared with cognitively normal older adults, and more than twice as likely to carry it compared with participants aged 80 or above who had Alzheimer’s dementia. This dual pattern of reduced risk genes and increased protective genes paints a powerful picture of genetic resilience.
This observational study drew on data from the Alzheimer’s Disease Sequencing Project Phenotype Harmonization Consortium and included 18,080 participants from eight national ageing cohorts. Super agers were identified in part by memory scores that exceeded the average performance of cognitively normal adults aged 50 to 64. The group represented multiple racial and ethnic backgrounds, alongside thousands of participants with Alzheimer’s dementia and cognitively healthy controls. Researchers believe these results strengthen the idea that studying super agers could reveal important biological mechanisms behind resistance to Alzheimer’s disease and healthy cognitive ageing more broadly.
More information: Alaina Durant et al, Evaluating the association of apolipoprotein E genotype and cognitive resilience in SuperAgers, Alzheimer’s & Dementia, The Journal of the Alzheimer’s Association. DOI: 10.1002/alz.71024
Journal information: Alzheimer’s & Dementia, The Journal of the Alzheimer’s Association Provided by Vanderbilt University Medical Center
