| Inheritance | Co-dominant (alongside APOE2 or APOE3) |
| Gene | APOE (Apolipoprotein E) |
| Chromosome | 19q13.32 |
| SNP ID | rs429358 (Arg130), rs7412 (Cys176) |
| Allele Frequency | ~15-20% in Caucasian populations; ~10-15% globally |
| Nucleotide Changes | C at rs429358 (Arg130), T at rs7412 (Cys176) |
| Increased lipid binding capacity | highest among all APOE isoforms |
| Domain interaction | N-terminal and C-terminal domains interact abnormally |
| Fragmentation susceptibility | prone to proteolytic cleavage generating neurotoxic fragments |
| Heterozygotes (E3/E4) | 3-4x increased risk compared to E3/E3 |
| Homozygotes (E4/E4) | 10-15x increased risk, with earlier onset (~65-70 years) |
| Population Attributable Risk | ~20-25% of AD cases attributable to APOE4 [3] |
| Databases | OMIMOrphanetClinicalTrialsPubMed |