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A novel antibody targeting sequence 31–35 in amyloid β protein attenuates Alzheimer's disease‐related neuronal damage
Author(s) -
Cheng Li,
Zhang Jun,
Li XinYi,
Yuan Li,
Pan YanFang,
Chen XiaoRong,
Gao TianMing,
Qiao JianTian,
Qi JinShun
Publication year - 2017
Publication title -
hippocampus
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.767
H-Index - 155
eISSN - 1098-1063
pISSN - 1050-9631
DOI - 10.1002/hipo.22676
Subject(s) - neuroscience , amyloid β , sequence (biology) , alzheimer's disease , antibody , amyloid (mycology) , disease , chemistry , medicine , biology , biochemistry , immunology , pathology , inorganic chemistry
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‐Aβ 31–35 antibody against Aβ 1–42 ‐induced impairments in neuronal viability, spatial memory, and hippocampal synaptic plasticity in rats. The results showed that the anti‐Aβ 31–35 antibody almost equally bound to both Aβ 31–35 and Aβ 1–42 , and pretreatment with the antibody dose‐dependently prevented Aβ 1–42 ‐induced cytotoxicity on cultured primary cortical neurons. In behavioral study, intracerebroventricular (i.c.v.) injection of anti‐Aβ 31–35 antibody efficiently attenuated Aβ 1–42 ‐induced impairments in spatial learning and memory of rats. In vivo electrophysiological experiments further indicated that Aβ 1–42 ‐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‐Aβ 31–35 antibody could be a novel immunotheraputic approach for the treatment of AD. © 2016 Wiley Periodicals, Inc.