A novel antibody targeting sequence 31-35 in amyloid β protein attenuates Alzheimer's disease-related neuronal damage.

Abstract

Amyloid β protein (Aβ) plays a critical role in pathogenesis of Alzheimer's disease (AD). Our previous studies indicated that the sequence 31-35 in Aβ molecule is an effective active center responsible for Aβ neurotoxicity in vivo and in vitro. In the present study, we prepared a novel antibody specifically targeting the sequence 31-35 of amyloid β protein, and investigated the neuroprotection of the anti-Aβ31-35 antibody against Aβ1-42 -induced impairments in neuronal viability, spatial memory, and hippocampal synaptic plasticity in rats. The results showed that the anti-Aβ31-35 antibody almost equally bound to both Aβ31-35 and Aβ1-42 , and pretreatment with the antibody dose-dependently prevented Aβ1-42 -induced cytotoxicity on cultured primary cortical neurons. In behavioral study, intracerebroventricular (i.c.v.) injection of anti-Aβ31-35 antibody efficiently attenuated Aβ1-42 -induced impairments in spatial learning and memory of rats. In vivo electrophysiological experiments further indicated that Aβ1-42 -induced suppression of hippocampal synaptic plasticity was effectively reversed by the antibody. These results demonstrated that the sequence 31-35 of Aβ may be a new therapeutic target, and the anti-Aβ31-35 antibody could be a novel immunotheraputic approach for the treatment of AD. © 2016 Wiley Periodicals, Inc.

• Authors: Li Cheng, Jun Zhang, Xin-Yi Li, Li Yuan, Yan-Fang Pan, Xiao-Rong Chen, Tian-Ming Gao, Jian-Tian Qiao, Jin-Shun Qi
• Journal: Hippocampus (Hippocampus) Vol. 27 Issue 2 Pg. 122-133 (02 2017) ISSN: 1098-1063 [Electronic] United States
• PMID: 27784133 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: © 2016 Wiley Periodicals, Inc.

Chemical References

• Amyloid beta-Peptides
• Antibodies
• Peptide Fragments
• amyloid beta-protein (1-42)
• amyloid beta-protein (31-35)

Topics

• Alzheimer Disease (metabolism, therapy)
• Amyloid beta-Peptides (antagonists & inhibitors, immunology, metabolism, toxicity)
• Animals
• Antibodies (immunology)
• CA1 Region, Hippocampal (physiology)
• Cell Survival
• Cells, Cultured
• Cerebral Cortex
• Disease Models, Animal
• Dose-Response Relationship, Immunologic
• Excitatory Postsynaptic Potentials (physiology)
• Immunotherapy
• Long-Term Potentiation (physiology)
• Male
• Maze Learning
• Neurons (physiology)
• Neuroprotection
• Peptide Fragments (antagonists & inhibitors, immunology, metabolism, toxicity)
• Rats, Wistar
• Spatial Memory