Prophylactic active immunization with a novel epitope vaccine improves cognitive ability by decreasing amyloid plaques and neuroinflammation in APP/PS1 transgenic mice

Publication date: Available online 19 January 2017
Source:Neuroscience Research
Author(s): Li Ding, Yuan Meng, Hui-Yi Zhang, Wen-Chao Yin, Yi Yan, Yun-Peng Cao
Both amyloid-β peptide (Aβ) deposition and neuroinflammation are considered to be early events that play pivotal roles in Alzheimer's disease (AD) pathogenesis and its associated cognitive impairment. Prophylactic anti-Aβ active immunotherapy is a promising therapeutic strategy for AD, if the Aβ-specific autoimmune responses to self T cell epitopes of Aβ can be avoided. This can be achieved by the use of antigen, which contains the B cell epitope of Aβ and excludes the Aβ-specific T cell epitope. In this study, we developed a novel peptide epitope vaccine, Aβ3-10-KLH, by coupling the B cell epitope Aβ3-10 to keyhole limpet hemocyanin (KLH) as the carrier protein, and subcutaneously injected it into 2.5-month-old APP/PS1 transgenic mice. Aβ3-10-KLH immunization induced high levels of anti-Aβ antibodies and significantly improved cognitive ability in APP/PS1 transgenic mice. Immunohistochemistry and immunofluorescence revealed that Aβ3-10-KLH immunization significantly reduced cerebral amyloid plaque formation and alleviated gliosis. The results indicate that Aβ3-10-KLH immunization successfully rescued cognitive impairment in APP/PS1 transgenic mice via decreasing cerebral Aβ deposition and neuroinflammation. Aβ3-10-KLH may potentially be safe and effective for prevention and treatment of AD.



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