Apolipoprotein E gene (APOE) (APOE)

The Apolipoprotein E (APOE) gene locus on chromosome 19 (19q13.32) is the primary genetic determinant of late-onset Alzheimer's disease (AD) risk (NIH, 2021). The gene exists in three common allelic variants—ε2, ε3, and ε4—which encode protein isoforms differing by single amino acids at positions 112 and 158 (Wikipedia, 2024). While the ε4 allele is a major risk factor for amyloid-beta accumulation and neurodegeneration, the ε3 allele is considered neutral, and the ε2 allele is significantly protective against AD and associated with increased longevity (PubMed, 2022). Therapeutic strategies targeting the APOE genomic DNA aim to leverage these differences through gene editing (e.g., CRISPR/Cas9 or base editing) to convert the high-risk ε4 allele into the protective ε2 or neutral ε3 variants (Nature Communications, 2021). Additionally, gene therapy strategies like LX1001 utilize adeno-associated viruses to deliver the protective APOE2 gene directly to the central nervous system of high-risk individuals (Lexeo Therapeutics, 2024). Beyond Alzheimer's, the APOE locus is essential for systemic and central lipid transport, and its variants are associated with cardiovascular diseases and lipid disorders like Type III hyperlipoproteinemia (MedlinePlus, 2021).

Other names

AD2LPGLDLCQ5Apolipoprotein E locusAPOE2APOE3APOE4rs429358rs7412

Gene replacement, gene editing, and base editing to modulate APOE isoform expression or convert high-risk alleles to protective variants.