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

摘要

Amyloid protein (A) plays a critical role in pathogenesis of Alzheimer's disease (AD). Our previous studies indicated that the sequence 31-35 in A molecule is an effective active center responsible for A neurotoxicity in vivo and in vitro. In the present study, we prepared a novel antibody specifically targeting the sequence 31-35 of amyloid protein, and investigated the neuroprotection of the anti-A(31-35) antibody against A(1-42)-induced impairments in neuronal viability, spatial memory, and hippocampal synaptic plasticity in rats. The results showed that the anti-A(31-35) antibody almost equally bound to both A(31-35) and A(1-42), and pretreatment with the antibody dose-dependently prevented A(1-42)-induced cytotoxicity on cultured primary cortical neurons. In behavioral study, intracerebroventricular (i.c.v.) injection of anti-A(31-35) antibody efficiently attenuated A(1-42)-induced impairments in spatial learning and memory of rats. In vivo electrophysiological experiments further indicated that A(1-42)-induced suppression of hippocampal synaptic plasticity was effectively reversed by the antibody. These results demonstrated that the sequence 31-35 of A may be a new therapeutic target, and the anti-A(31-35) antibody could be a novel immunotheraputic approach for the treatment of AD. (c) 2016 Wiley Periodicals, Inc.