Most of our genomes carry more or less the same genes, but there may be small variations in the sequences of those genes that can have a variety of effects. Some genetic variants have mild or negligible effects, while others can have a major influence on our health; some can even cause serious diseases. There are a few variants of the APOE gene, for example. One APOE variant has been repeatedly linked to dramatic increases in the risk of Alzheimer’s disease: APOE-ε4 (or just APOE4). Another APOE variant known as APOE-ε2 (APOE2) can actually have a protective effect against Alzheimer’s disease (AD).
Now, scientists have found that APOE variants can also have a significant impact on how people age cognitively. This work included data from 18,080 individuals who were part of eight national aging cohorts that represented several racial and ethnic groups. The findings have been reported in Alzheimer's & Dementia.
In this study, the researchers analyzed how often APOE4 and APOE2 variants arose in people who were considered to be ‘super-agers': people who were aged 80 or older but had cognitive abilities that were, on average, better than individuals aged 50 to 64. Cognitive ability was assessed using memory tests.
The investigators determined that super-agers were 68% less likely to carry an APOE4 variant, compared to people who were 80 or older but had dementia at that point. Super-agers were also found to be 19% less likely to carry APOE4 then people who were cognitively normal in that 80 or older age group.
"This was our most striking finding—although all adults who reach the age of 80 without receiving a diagnosis of clinical dementia exhibit exceptional aging, our study suggests that the super-ager phenotype can be used to identify a particularly exceptional group of oldest-old adults with a reduced genetic risk for Alzheimer's disease," explained corresponding study author Leslie Gaynor, Ph.D., an assistant professor at Vanderbilt University.
The data also showed that APOE2 arises more often in super-agers; APOE2 variants were 28% in super-agers compared to others who were 80 and older but cognitively normal for their age; the super-agers were also 103% more likely to carry APOE2 compared to others in the same age group who had also been diagnosed with AD.
"With interest in super-agers growing, our findings notably encourage the view that the super-ager phenotype will prove useful in the continued search for mechanisms conferring resilience to AD,” said Gaynor.
"This is by far the largest study to date to identify differences in APOE-ε4 allele frequency based on super-ager status, and the first study to find a relationship between APOE-ε2 allele frequency and super-ager status. We would expect these findings to lend continued interest to questions of how these variants may influence development of clinical dementia due to Alzheimer's disease, as well as to the super-ager phenotype more generally."
Sources: Vanderbilt University Medical Center, Alzheimer’s & Dementia