Abstract: Non-enzymatic isomerization of aspartic acid residues in proteins associated with Alzheimer’s disease: Proteins are composed of L-amino acids following ribosomal translation. However, if they remain unmetabolized for an extended period, some residues (particularly aspartic acid [Asp]) undergo isomerization to the D-form. This process begins with nucleophilic attack (by the nitrogen atom of the amide group of an adjacent residue) on the side-chain carboxy group of an Asp residue. This forms a fivemembered L-succinimide intermediate, which has two carbonyl carbons and can transform back to an L-Asp residue or isomerize into an L-isoAsp residue. The chiral center of the L-succinimide intermediate can easily invert to form a D-succinimide intermediate via keto-enol tautomerization. This D-succinimide intermediate then cleaves to yield a D-aspartic acid (D-Asp) or D-isoaspartate (D-isoAsp) residue.