Protective Effects against the Development of Alzheimer’s Disease in an Animal Model through Active Immunization with Methionine-Sulfoxide Rich Protein Antigen

• Published in: Antioxidants
• Main Authors: Adam S. Smith, Kyle R. Gossman, Benjamin Dykstra, Fei Philip Gao, Jackob Moskovitz
• Format: Article
• Language: English
• Published: MDPI AG 2022-04-01
• Subjects: methionine oxidation; active immunization; Alzheimer’s disease; oxidative stress
• Online Access: https://www.mdpi.com/2076-3921/11/4/775

The brain during Alzheimer’s disease (AD) is under severe oxidative attack by reactive oxygen species that may lead to methionine oxidation. Oxidation of the sole methionine (Met35) of beta-amyloid (A<i>β</i>), and possibly methionine residues of other extracellular proteins, may be one of the earliest events contributing to the toxicity of A<i>β</i> and other proteins in vivo. In the current study, we immunized transgenic AD (APP/PS1) mice at 4 months of age with a recombinant methionine sulfoxide (MetO)-rich protein from <i>Zea mays</i> (antigen). This treatment induced the production of anti-MetO antibody in blood-plasma that exhibits a significant titer up to at least 10 months of age. Compared to the control mice, the antigen-injected mice exhibited the following significant phenotypes at 10 months of age: better short and long memory capabilities; reduced A<i>β</i> levels in both blood-plasma and brain; reduced A<i>β</i> burden and MetO accumulations in astrocytes in hippocampal and cortical regions; reduced levels of activated microglia; and elevated antioxidant capabilities (through enhanced nuclear localization of the transcription factor Nrf2) in the same brain regions. These data collected in a preclinical AD model are likely translational, showing that active immunization could give a possibility of delaying or preventing AD onset. This study represents a first step toward the complex way of starting clinical trials in humans and conducting the further confirmations that are needed to go in this direction.