Apolipoprotein E (APOE) ε4 is associated with younger age at ischemic stroke onset but not with stroke outcomes, according to study results published in Neurology.

Previous studies have shown that APOE genotype is a predictor of outcome after hemorrhagic stroke, but there are conflicting data regarding the effect of this genotype on ischemic stroke. In the current study, researchers investigated the interplay among the 3 common APOE alleles (ε2, ε3, and ε4), age at ischemic stroke onset, severity, sex, and outcome.

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The study cohort included 6165 cases from the genome-wide association study within the Genetics of Ischemic Stroke Functional Outcome network. Effects of APOE allele ε4 and ε2 were compared with those of the most common allele, ε3.

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The study revealed an association between increasing allele count of ε4 and younger age at stroke onset (P <.001), which was evident in both sexes and in cases with first-stroke only. However, there was no evidence for direct effect of ε4 on outcome after stroke as, following adjustment for age and stroke severity, there was no association between ε4 allele count and favorable outcome. In men only, there was a statistically significant association between ε2 allele count and poor outcomes following adjustment for ancestry, age, and stroke severity.

The researchers acknowledged several study limitations, including those of Genetics of Ischemic Stroke Functional Outcome study that were previously reported, as well as the relatively small sample size for the sex-stratified analyses and use of imputed values from single nucleotide polymorphism arrays to establish common APOE alleles.

“This study shows that APOE ε4 carriers have a younger age at ischemic stroke onset. We also detected worse functional outcome in male ε2 carriers, a result needing replication,” concluded the researchers.


Lagging C, Lorentzen E, Stanne TM, et al. APOE ε4 is associated with younger age at ischemic stroke onset but not with stroke outcome. Neurology. 2019;93:849-853