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

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 antibody against Aβ -induced impairments in neuronal viability, spatial memory, and hippocampal synaptic plasticity in rats. The results showed that the anti-Aβ antibody almost equally bound to both Aβ and Aβ , and pretreatment with the antibody dose-dependently prevented Aβ -induced cytotoxicity on cultured primary cortical neurons. In behavioral study, intracerebroventricular (i.c.v.) injection of anti-Aβ antibody efficiently attenuated Aβ -induced impairments in spatial learning and memory of rats. In vivo electrophysiological experiments further indicated that Aβ -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 antibody could be a novel immunotheraputic approach for the treatment of AD. © 2016 Wiley Periodicals, Inc.