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Prophylactic Vaccine Based on Pyroglutamate-3 Amyloid β Generates Strong Antibody Response and Rescues Cognitive Decline in Alzheimer's Disease Model Mice.
ACS Chem Neurosci 2017; 8(3):454-459AC

Abstract

Clearance of amyloid β (Aβ) by immunotherapy is one of the fancy methods to treat Alzheimer's disease (AD). However, the failure of some clinical trials suggested that there may be something ignored in the past development of immunotherapy. Pyroglutamate-3 Aβ (AβpE3-X), which was found to be abundant in the patients' brain, has attracted much attention after the report that AβpE3-42 could serve as a template to exacerbate the aggregation of Aβ. In addition, AβpE3-X could not be recognized by the antibodies targeting the N-terminus of Aβ, suggesting that AβpE3-X maybe the ignored one. Indeed, passive immunization targeting AβpE3-X has shown some beneficial results, while active immunotherapy has not been extensively studied. In the present study, we designed and synthesized a novel peptide vaccine targeting AβpE3-X, which contains AβpE3-15 as B cell epitope and P2 as T cell epitope. We showed that this vaccine could induce strong antibody response to AβpE3-X. We also showed that prophylactic immunization of AD model mice with our vaccine could reduce Aβ plaques and rescue cognitive decline. This new kind of Aβ vaccine will open up new directions for AD immunotherapy.

Authors+Show Affiliations

Key Laboratory of Bioorganic Phosphorus Chemistry and Chemical Biology (Ministry of Education), Department of Chemistry, Tsinghua University , Beijing 100084, China.Key Laboratory of Bioorganic Phosphorus Chemistry and Chemical Biology (Ministry of Education), Department of Chemistry, Tsinghua University , Beijing 100084, China.Key Laboratory of Bioorganic Phosphorus Chemistry and Chemical Biology (Ministry of Education), Department of Chemistry, Tsinghua University , Beijing 100084, China.Key Laboratory of Bioorganic Phosphorus Chemistry and Chemical Biology (Ministry of Education), Department of Chemistry, Tsinghua University , Beijing 100084, China.Key Laboratory of Bioorganic Phosphorus Chemistry and Chemical Biology (Ministry of Education), Department of Chemistry, Tsinghua University , Beijing 100084, China.Key Laboratory of Bioorganic Phosphorus Chemistry and Chemical Biology (Ministry of Education), Department of Chemistry, Tsinghua University , Beijing 100084, China.Key Laboratory of Bioorganic Phosphorus Chemistry and Chemical Biology (Ministry of Education), Department of Chemistry, Tsinghua University , Beijing 100084, China. Beijing Institute for Brain Disorders , Beijing 100069, China.

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

28292186

Citation

Li, Gao, et al. "Prophylactic Vaccine Based On Pyroglutamate-3 Amyloid Β Generates Strong Antibody Response and Rescues Cognitive Decline in Alzheimer's Disease Model Mice." ACS Chemical Neuroscience, vol. 8, no. 3, 2017, pp. 454-459.
Li G, Hu ZW, Chen PG, et al. Prophylactic Vaccine Based on Pyroglutamate-3 Amyloid β Generates Strong Antibody Response and Rescues Cognitive Decline in Alzheimer's Disease Model Mice. ACS Chem Neurosci. 2017;8(3):454-459.
Li, G., Hu, Z. W., Chen, P. G., Sun, Z. Y., Chen, Y. X., Zhao, Y. F., & Li, Y. M. (2017). Prophylactic Vaccine Based on Pyroglutamate-3 Amyloid β Generates Strong Antibody Response and Rescues Cognitive Decline in Alzheimer's Disease Model Mice. ACS Chemical Neuroscience, 8(3), pp. 454-459. doi:10.1021/acschemneuro.6b00336.
Li G, et al. Prophylactic Vaccine Based On Pyroglutamate-3 Amyloid Β Generates Strong Antibody Response and Rescues Cognitive Decline in Alzheimer's Disease Model Mice. ACS Chem Neurosci. 2017 03 15;8(3):454-459. PubMed PMID: 28292186.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Prophylactic Vaccine Based on Pyroglutamate-3 Amyloid β Generates Strong Antibody Response and Rescues Cognitive Decline in Alzheimer's Disease Model Mice. AU - Li,Gao, AU - Hu,Zhi-Wen, AU - Chen,Pu-Guang, AU - Sun,Zhan-Yi, AU - Chen,Yong-Xiang, AU - Zhao,Yu-Fen, AU - Li,Yan-Mei, Y1 - 2016/11/29/ PY - 2017/3/16/entrez PY - 2017/3/16/pubmed PY - 2017/10/27/medline KW - Alzheimer’s disease (AD) KW - Aβ plaques KW - prophylactic immunization KW - pyroglutamate-3 Aβ KW - vaccine SP - 454 EP - 459 JF - ACS chemical neuroscience JO - ACS Chem Neurosci VL - 8 IS - 3 N2 - Clearance of amyloid β (Aβ) by immunotherapy is one of the fancy methods to treat Alzheimer's disease (AD). However, the failure of some clinical trials suggested that there may be something ignored in the past development of immunotherapy. Pyroglutamate-3 Aβ (AβpE3-X), which was found to be abundant in the patients' brain, has attracted much attention after the report that AβpE3-42 could serve as a template to exacerbate the aggregation of Aβ. In addition, AβpE3-X could not be recognized by the antibodies targeting the N-terminus of Aβ, suggesting that AβpE3-X maybe the ignored one. Indeed, passive immunization targeting AβpE3-X has shown some beneficial results, while active immunotherapy has not been extensively studied. In the present study, we designed and synthesized a novel peptide vaccine targeting AβpE3-X, which contains AβpE3-15 as B cell epitope and P2 as T cell epitope. We showed that this vaccine could induce strong antibody response to AβpE3-X. We also showed that prophylactic immunization of AD model mice with our vaccine could reduce Aβ plaques and rescue cognitive decline. This new kind of Aβ vaccine will open up new directions for AD immunotherapy. SN - 1948-7193 UR - https://www.unboundmedicine.com/medline/citation/28292186/Prophylactic_Vaccine_Based_on_Pyroglutamate_3_Amyloid_β_Generates_Strong_Antibody_Response_and_Rescues_Cognitive_Decline_in_Alzheimer's_Disease_Model_Mice_ L2 - https://dx.doi.org/10.1021/acschemneuro.6b00336 DB - PRIME DP - Unbound Medicine ER -