Christina Phan

Introduction: Alzheimer’s disease (AD) is a type of dementia that typically occurs in adults older than 65 years of age,characterized symptomatically with the progressive loss of cognitive function and psychiatric manifestations. The depositions of plaques consisting of insoluble amyloid beta (AB) fibrils, are one of the major pathological hallmarks of AD, causing neuronal and synaptic cell loss and damage.² Studies focusing on the use of anti (AB) antibodies as a preventative and therapeutic treatment in mice models demonstrate its ability to clear the plaques, induce the body to develop a persisting repertoire of anti AB antibody, and reduce neuroinflammation.⁴ These findings suggest a promising future for the prevention and treatment of AD. Methods: APP/PS1 transgenic mice models were used. The mice were injected with an epitope vaccine created using the 3-10 amino acid region of the neurotoxic Aβ 1-42 peptide conjugated to the immunogenic carrier protein keyhole limpet hemocyanin.¹ ELISA analysis was used to determine serum anti AB antibody concentration and isotypes. Reduction of the the AB burden was visualized using immunohistochemical detection and light microscopy. Results were compared between mice immunized with AB 3-10 KLH, saline, and WT¹. Microglial dysfunction and its role in AB 3-10 KLH decreased efficacy were studied using TREM2 knock out mice.³ A plaque clearance assay was used to assess the activity of microglial phagocytosis between TREM2 knockout and WT mice. Results: Mice immunized with AB3-10 KLH showed detectable titers of anti Aβ antibody by the second vaccination using ELISA. Antibody levels reached an average of 127.60 ± 22.16 after the last immunization with the main type of antibody being induced being IgG1.Quantification of Aβ deposition in AB3-10 KLH immunized mice showed that the number of amyloid plaques in the hippocampus and cortex decreased 39.76% and 4.32% respectively.¹ Immunization reduced GFAP-positive cells in the hippocampus and cortex to 76.9% and 72.5% respectively.³ Conclusion: Studies in mice models show that immunization with AB 3-10 KLH was able to induce a significant amount of anti AB antibody, which was effective in the clearance of amyloid plaques and reducing neuroinflammation.¹ Deficiency in microglial genes were shown to hinder the efficacy of AB 3-10 KLH, but in wild type mice, normal functioning microglia were able to phgagocytize and clear anti AB antibody bound amyloid plaques.³

1.  Li Ding, Yuan Meng, Hui-Yi Zhang, Wen-Chao Yin, Yi Yan, Yun-Peng Cao, Active immunization with the peptide epitope vaccine Aβ3-10-KLH induces a Th2-polarized anti-Aβ antibody response and decreases amyloid plaques in APP/PS1 transgenic mice, Neuroscience Letters, Volume 634, 10 November 2016, Pages 1-6, ISSN 0304-3940, http://doi.org/10.1016/j.neulet.2016.09.050.
2. Lacor, Pascale N., Maria C. Buniel, Paul W. Furlow, Antonio Sanz Clemente, Pauline T. Velasco, Margaret Wood, Kirsten L. Viola, and William L. Klein. “Aβ Oligomer-Induced Aberrations in Synapse Composition, Shape, and Density Provide a Molecular Basis for Loss of Connectivity in Alzheimer’s Disease.” Journal of Neuroscience. Society for Neuroscience, 24 Jan. 2007. Web. 24 Apr. 2017.
3. Xiang, Xianyuan, Georg Werner, Bernd Bohrmann, Arthur Liesz, Fargol Mazaheri, Anja Capell, Regina Feederle, Irene Knuesel, Gernot Kleinberger, and Christian Haass. “TREM2 Deficiency Reduces the Efficacy of Immunotherapeutic Amyloid Clearance.” EMBO Molecular Medicine. EMBO Press,08 July 2016. Web. 05 June 2017.
4. Ding, Li, Yuan Meng, Hui-Yi Zhang, Wen-Chao Yin, Yi Yan, and Yun-Peng Cao. “Prophylactic Active Immunization with a Novel Epitope Vaccine Improves Cognitive Ability by Decreasing Amyloid Plaques and Neuroinflammation in APP/PS1 Transgenic Mice.” ScienceDirect. Elsevier, 19 Jan.2017. Web. 05 June 2017.