BS in Biochemistry
Chemistry and Biochemistry Department
Purpose: Alzheimer’s Disease is a neurodegenerative disease resulting from over-production and neuronal accumulation of amyloid-beta proteins (Aβ40/Aβ42). The glycine residue at position 33 and histidine residues at positions 13 and 14 are involved with binding and internalization of these proteins, actions potentially inhibited by substituting or sterically hindering these residues with an antibody specific to positions 2-11 (IgG-4.1). Rat pheochromocytoma (PC12) cells differentiated with nerve growth factor were used as a neuronal model to determine whether substitution and/or antibody block amyloid-beta’s neuronal interactions.
Methods: PC12 cells were incubated with fluorescein-labeled-amyloid-beta-40 (F-Aβ40) or substituted F-Aβ40 derivatives (F-Aβ40-H13,14G, F-Aβ40-H13,14G;G33A), with or without IgG-4.1. Cells were analyzed by flow cytometry.
Results: PC12 cells incubated with F-Aβ40 and IgG-4.1, as well as cells incubated with substituted peptides, exhibit decreased mean fluorescence compared to cells incubated with F-Aβ40 alone.
Conclusion: IgG-4.1 and amino acid substitution decreased binding and internalization of Aβ40, suggesting immunotherapy may reduce intraneuronal accumulation of amyloid-beta.