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.