The three isoforms differ from each other by replacing one or two amino acids at positions 112 and 158, as follows: ApoE2 has a cysteine residue at both positions; ApoE3 has an arginine at position 158; while type 4 has an arginine residue at both positions.(76) The polymorphisms presented by the ApoE protein are the primary genetic risk factor for AD development. This evidence concerns the gene APOE and Alzheimer disease.