Beliefs about aging affect expression of gene associated with Alzheimer’s

written by Sue Frantz | September 10, 2025

This is the fifth in a series of posts based on Becca Levy’s book Breaking the age code: How your beliefs about aging determine how long & well you live.

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Our risk of developing late-onset Alzheimer’s disease is influenced by the apolipoprotein E (APOE) gene. The three most common variants of the gene are ε2, ε3, and ε4. The e2 variant, which occurs in about 10% of the population (B. Levy, 2022), is protective. It reduces our risk of developing Alzheimer’s. The ε3 variant is the most common, and it seems to have no impact on developing Alzheimer’s. The ε4 variant, which occurs in 15% to 25% of the population (ALZinfo.org, 2024), however, increases our risk and is associated with more severe symptoms (Mayo Clinic Staff, 2025). “Having at least one APOE ε4 variant doubles or triples the risk of getting Alzheimer’s disease. Having two APOE ε4 variants increases that risk even more. Someone with two APOE ε4 variants is 8 to 12 times more likely to develop Alzheimer’s disease” (Mayo Clinic Staff, 2025). That’s sobering.

While having APOE ε4 increases our risk for Alzheimer’s, it doesn’t guarantee we will develop it. Becca Levy wondered if positive age beliefs could be one reason why. She and her colleagues analyzed the data from 4,765 people who were 60 years old or older and who showed no signs of dementia at baseline. Through genetic testing, they found that 26% of their participants (n=1,250) had at least one APOE ε4 variant (the one that increases risk). Four years later, some of the participants in the survey had developed symptoms of dementia. But get this. “Among those with APOE ε4, those with positive age beliefs were 49.8% less likely to develop dementia than those with negative age beliefs” (B. R. Levy et al., 2018, p. 1). Reread that sentence. That is nothing short of astounding. One explanation Levy offers is that the culprit may ultimately be stress (B. Levy, 2022). If we believe that aging will be a horrific experience, each passing year will be dreaded more than the last. I can see where that would wear on a person. However, if we believe that aging will be a positive experience, each passing year will be welcomed as an additional year of wisdom and experience. Positive age beliefs may flip the epigenetic switch such that the APOE ε4 gene expression is turned off (B. R. Levy et al., 2018).

Levy wondered if positive age beliefs could boost the protective effects of the APOE ε2 gene. She and her colleagues analyzed the data from 3,895 people who were 60 years old or older and who had 8 years’ worth of cognitive assessments. From this group, they found 13% (n=490) had at least one APOE ε2 variant (the one that decreases risk for Alzheimer’s disease). While positive age beliefs were associated with stronger cognition scores for those who did not have the ε2 variant, positive age beliefs were associated with even stronger cognition scores for those who had the ε2 variant (B. R. Levy et al., 2020).

Regardless of which APOE variant we have, positive age beliefs benefit us. The more I read about positive age beliefs, the more convinced I am that we need to scrub the ageist crap from our interactions with our students, our family, our friends, our casual acquaintances, and our own self-talk.

References

ALZinfo.org. (2024, May 15). A new genetic form of Alzheimer’s disease? Fisher Center for Alzheimer’s Research Foundation. https://www.alzinfo.org/articles/diagnosis/a-new-genetic-form-of-alzheimers-disease/

Levy, B. (2022). Breaking the age code: How your beliefs about aging determine how long & well you live (First edition). William Morrow, an imprint of HarperCollins Publishers.

Levy, B. R., Slade, M. D., Pietrzak, R. H., & Ferrucci, L. (2018). Positive age beliefs protect against dementia even among elders with high-risk gene. PLOS ONE, 13(2), e0191004. https://doi.org/10.1371/journal.pone.0191004

Levy, B. R., Slade, M. D., Pietrzak, R. H., & Ferrucci, L. (2020). When culture influences genes: Positive age beliefs amplify the cognitive-aging benefit of APOE ε2. The Journals of Gerontology: Series B, 75(8), e198–e203. https://doi.org/10.1093/geronb/gbaa126

Mayo Clinic Staff. (2025, April 24). The role of genes in your Alzheimer’s risk. Mayo Clinic. https://www.mayoclinic.org/diseases-conditions/alzheimers-disease/in-depth/alzheimers-genes/art-20046552