ApoE genotype accounts for the vast majority of AD risk and AD pathology

In this review, evidence is provided that apolipoprotein E (apoE) genotype accounts for the majority of Alzheimer’s disease (AD) risk and pathology. The three major human isoforms, apoE2, apoE3, and apoE4, are encoded by different alleles (var epsilon2, var epsilon3, var epsilon4) and regulate lipid metabolism and redistribution. ApoE isoforms differ in their effects on AD risk and pathology. Clinical and epidemiological data have indicated that the var epsilon4 allele may account for 50% of AD in the United States. Further, the rarity of AD among carriers of the var epsilon2 allele suggests that allelic variations in the gene encoding this protein may account for over 95% of AD cases. ApoE4 disrupts memory function in rodents. Further studies have indicated that fragments of apoE may contribute to both plaque and tangle formation. Thus, the epidemiologic and basic science evidence suggest that apoE genotype accounts for the vast majority of AD risk and pathology.