What We Know, and Don’t Know, About Genetics, Alzheimer’s and Aging

Key Takeaways SuperAgers are adults aged 80 and older whose memory matches that of people decades younger. Different variants in the APOE gene can impact the likelihood of Alzheimer’s. The e4 variant is associated with higher likelihood while the e2 variant is associated with lower likelihood and is more common in people who reach very old age. There’s much we still don’t know about healthy aging. A 2026 study found SuperAgers were no more likely to have the APOE e2 variant, and their Alzheimer’s polygenic risk scores looked essentially the same as cognitively healthy peers.

Imagine hearing a list of 15 unrelated words, spending the next 20 minutes on something else, then recalling nine or more of them. That is a strong performance for someone in their late 50s. Now imagine doing it in your 80s. A small group of older adults can, and researchers call them SuperAgers. Are these people simply genetically lucky? A study published in July 2026 suggests the answer is more complicated than that.

How Does the APOE Gene Affect Alzheimer’s Risk?

The APOE gene is the strongest common genetic influence on late-onset Alzheimer’s disease, and it typically comes in three versions that push risk in different directions. 

The e3 version is the most common and is considered neutral. The e4 version increases the likelihood of developing Alzheimer’s and is linked to an earlier age of onset. About 25% of people carry one copy of e4 and 2–3% carry two copies. People with two copies have been estimated to have up to a 60% chance of developing Alzheimer’s by age 85 compared to a risk of about 10% in the general population.

The e2 version is the least common, but it has been associated with a lower likelihood of developing Alzheimer’s. It also shows up more often in people who live exceptionally long lives. In an analysis of 28,297 participants across seven studies of aging, carrying a single copy of e2 was associated with greater odds of reaching extreme old age.

One important caveat runs through all of this. Most genetic studies and risk estimates for Alzheimer’s disease come from studies of people of European descent. How well those numbers transfer to people of other ancestries remains an open question, even as Alzheimer’s disproportionately affects Black and Hispanic Americans.

How Might APOE e2 Protect Neurons?

New laboratory research suggests e2 may help neurons protect their own DNA. Researchers grew human neurons from stem cells that were genetically identical except at the APOE gene, then compared them. Neurons carrying the e2 variant showed lower levels of DNA damage and were more resistant to becoming senescent, a state in which cells stop functioning normally but do not die, after being exposed to stress compared to neurons carrying the e4 variant. The team saw similar patterns in the brains of aged mice carrying human e2 and e4 variants of the APOE gene.

Notably, adding purified e2 APOE protein to neurons that had the e4 genetic variant reduced DNA damage signaling, which hints that some of the protection may come from the APOE protein itself. It’s important to remember this was observed in cells and mice. It is not a treatment, and the researchers are clear that the precise molecular steps still need to be worked out.

Do SuperAgers Have More Protective Genetics?

Here is where the story turns. If e2 lowers the chances of Alzheimer’s and e4 raises it, you might expect more SuperAgers to have the e2 variant and few would have e4. That’s not what researchers found.

They compared the DNA of 142 SuperAgers and 89 cognitively healthy adults of similar age. 12.7% of SuperAgers and 13.1% of controls had at least one copy of the e2 variant. The proportion carrying at least one e4 variant was 15.7% and 19.0%. Neither difference was statistically significant. 

Researchers also calculated three different Alzheimer’s polygenic risk scores, which combine the small effects of many common variants into a single estimate of genetic likelihood, and found no meaningful difference between the groups. A handful of SuperAgers even carried two copies of e4 or had high polygenic risk scores and still had youthful memory.

In other words, genetic variants that impact your chances of getting Alzheimer’s, including e2, e4 and other common genetic risk factors, don’t change your chance of having the memory of a 60-year-old at age 85. 

What This Study Cannot Tell Us Yet

Does this mean that APOE doesn’t actually matter? No. The APOE e4 variant remains the strongest common genetic influence on late-onset Alzheimer’s that researchers have found, and nothing in this study challenges that. What the study asked was a narrower question: whether APOE and other common variants explain why some people keep exceptional memory into their 80s. 

This was a small study, and that is not a flaw so much as a reality of the field. People who live well into their 80s with the memory of a 60-year-old are rare, which makes them hard to recruit in large numbers. The SuperAging analysis was also a snapshot in time rather than a study that followed people as they aged, and it did not measure vascular health, physical activity, sleep or other lifestyle factors that may matter a great deal. 

So the question remains open: what influences your chances of healthy aging? Other genetic factors, lifestyle, environment and probably some combination of all three. Answering this question will require more research and participation from larger and more diverse groups of individuals.

Curious about your own APOE variants? 23andMe’s Late-Onset Alzheimer’s Disease Genetic Health Risk report* can tell you if you carry the e4 variant, and Premium Ancestry + Total Health members can see if they carry other APOE variants through exome sequencing. 

* The 23andMe PGS test uses qualitative genotyping to detect select clinically relevant variants in the genomic DNA of adults from saliva for the purpose of reporting and interpreting genetic health risks. It is not intended to diagnose any disease. Your ethnicity may affect the relevance of each report and how your genetic health risk results are interpreted. Each genetic health risk report describes if a person has variants associated with a higher risk of developing a disease, but does not describe a person’s overall risk of developing the disease. The test is  not intended to tell you anything about your current state of health, or to be used to make medical decisions, including whether or not you should take a medication, how much of a medication you should take, or determine any treatment.  

The Late-Onset Alzheimer’s Disease genetic health risk report is indicated for reporting of the e4 variant in the APOE gene and describes if a person has a variant associated with an increased risk of developing late-onset Alzheimer’s disease. The e4 variant included in this report is found and has been studied in many ethnicities. Detailed risk estimates have been studied the most in people of European descent.