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APOE4 Genetic Variants and Alzheimer’s Disease

May 2024 Study Explores Alzheimer's Risk in APOE4 Homozygotes


Medical News

Alzheimer's, APOE4 homozygotes

A study published in May, 2024, using data from 10,039 individuals and 3,297 brain donors from the National Alzheimer’s Coordinating Center looked at the risk of Alzheimer’s disease in APOE4 genetic variant homozygotes. 


APOE4 homozygotes have been reported in past studies to have a lifetime risk for Alzheimer’s disease of up to 60% by age 85.  The authors reported that this study compared APOE4 homozygotes to subjects who had the more common APOE3 variant that is not associated with Alzheimer’s disease. 


On average, Alzheimer’s disease symptoms for the APOE4 group started at age 65.6, produced cognitive defects at age 71.8, dementia at age 73.6 and death at 77.2, about 7–10 years earlier than those who developed Alzheimer’s disease and did not carry the APOE4 variant.  APOE4 homozygotes had significantly higher levels of Alzheimer’s biomarkers in their blood from age 55 on, compared to normal variant individuals.  By age 65, over 90% had abnormal amyloid levels in their cerebrospinal fluid and 75% had positive scans for amyloid.  The authors also stated that APOE4 homozygotes and heterozygotes have very different clinical outcomes and genetic risk profiles and should not be thought of as a single entity.  


Summary

Besides being found to have an increased risk for dementia-related death in the previously discussed olive oil study, APOE4 homozygote individuals are at a very high risk for Alzheimer’s disease.  The authors suggested that it is in fact more than just a risk factor but should be considered a genetic form of Alzheimer’s disease.  Although there are racial and geographical variations, the incidence of APOE4 homozygotes is thought to be about 2% of the population.  The study’s authors stated that their findings pointed to the need for individualized prevention strategies and more research to find effective treatments. 


Resources

Fortea, J., Pegueroles, J., Alcolea, D. et al. APOE4 homozygozity represents a distinct genetic form of Alzheimer’s disease. Nat Med (2024). Retrieved from: https://www.nature.com/articles/s41591-024-02931-w#citeas

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