Administration of amyloid-β42 oligomer-specific monoclonal antibody improved memory performance in SAMP8 mice.

Amyloid-β peptide (Aβ) is recognized by many as the leading cause of Alzheimer's disease (AD), and Aβ oligomers play a major role in the early-onset form of AD. Recently, the application of passive immunization targeting Aβ has been investigated as a potential method of AD immunotherapy. We used a strain of monoclonal antibody against Aβ42 oligomers, designated A8, as an Aβ inhibitor to suppress Aβ aggregation and Aβ-derived cell toxicity in vitro, and as a passive immunotherapy approach to treat SAMP8 (senescence accelerated mouse sub-line P8) mice, an animal model of AD, in vivo. First, our results showed that pre-incubation of A8 with Aβ oligomers inhibited both the maturation of Aβ fiber and Aβ oligomer toxicity on SH-SY5Y cells. Second, learning and memory was improved through intraperitoneal administration of A8 in SAMP8 mice. Third, Aβ pathology was ameliorated with decreased Aβ oligomers and phospho-tau levels in SAMP8 mice. Our data suggest that our monoclonal antibody A8 may be a candidate as a potential immunotherapeutic agent in AD.