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ApoE: A new piece to the severe malaria puzzle

Pediatric Research (2024)Cite this article

Apolipoprotein E (apoE), encoded by the APOE gene, is a protein found throughout the body that facilitates lipid transport, particularly in the blood and central nervous system, via binding to the low-density lipoprotein receptor.1 The three major isoforms of apoE - apoE2, apoE3, and apoE4 - differ by single amino acid substitutions at two sites; apoE3 is the most common isoform. The different APOE alleles play a role in vulnerability to several diseases, particularly ones with a neurological component. APOE4 has been associated with poor outcomes in individuals with acute head trauma and stroke, whereas APOE2 has a protective effect in neurodegenerative disease.1 These associations are likely due to allelic differences in lipid transport capability and the neuronal repair process.

In this issue, Lima-Cooper et al. focused on APOE polymorphisms among Ugandan children in a large severe malaria case-control study. The APOE4 allele was more common among children with cerebral malaria or severe malarial anemia compared to healthy controls, suggesting that it increased the risk of particular severe malaria subtypes. APOE4 was also associated with increased mortality in cerebral malaria and with a higher risk of post-discharge malaria. The APOE3 allele was found more frequently in community controls compared to children with severe malaria, but this finding was not statistically significant. Furthermore, children with cerebral malaria and the APOE3 allele had a significantly reduced risk of post-discharge clinical malaria.

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  1. Center for Vaccine Development and Global Health, University of Maryland School of Medicine, Baltimore, MD, USA

    Emily M. Stucke, Jonathan G. Lawton & Mark A. Travassos

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  1. Emily M. Stucke
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Correspondence to Mark A. Travassos.

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Stucke, E.M., Lawton, J.G. & Travassos, M.A. ApoE: A new piece to the severe malaria puzzle. Pediatr Res (2024). https://doi.org/10.1038/s41390-024-03096-5

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