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Editorial
May 31, 2022

Rare APOE Missense Variants—Can We Overcome APOE ε4 and Alzheimer Disease Risk?

Author Affiliations
  • 1Department of Neurology, Weill Institute for Neurosciences, University of California, San Francisco, San Francisco
  • 2Memory and Aging Center, University of California, San Francisco, San Francisco
  • 3Department of Radiology and Biomedical Imaging, University of California, San Francisco, San Francisco
  • 4Associate Editor, JAMA Neurology
JAMA Neurol. 2022;79(7):649-651. doi:10.1001/jamaneurol.2022.0854

Everyone carries at least 1 of 3 main alleles of the apolipoprotein E (APOE) gene: APOE ε2, APOE ε3, or APOE ε4. The APOE alleles encode 3 protein isoforms that differ at just 2 amino acid positions (positions 112 and 158) (Figure). How these small protein changes can lead to large effects on brain health is a high value area of fervent investigation, with exciting therapeutic implications for Alzheimer disease (AD).

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