Targeting Ab Oligomers Figure 3. A complex between Ab oligomers and OMAB display very slow dissociation rate. Different samples of Ab(1–40) and Ab(1–42) was separated by SEC. (A) The Ab(1–40) monomeric fraction or (B) Ab(1–40) the oligomeric or (C) monomeric fraction of Ab(1–42) or (D) Ab(1–42) the oligomeric fraction were analyzed for binding to OMAB, immobilized to a CM5 chip. The dissociation of (A) monomeric Ab(1–40) was fitted to a single exponential decay (red line) with a rate constant of 0.0092 s and a T1/2 of 75 s, and of (B)(1–40) oligomeric Ab to a double exponential decay (red line) with rate constants of 0.016 and 1.88 * 10-6, and with a T1/2 of 42 s and 4.2 days, respectively. (C) monomeric Ab(1–42) was fitted to a single exponential decay (red line) with a rate constant of 0.012 s and a T1/2 of 57 s for the oligomeric fraction of Ab1-42 (D) no dissociation was detected due to a to very strong interaction. All experiments were performed in PBS at 25uC. doi:10.1371/journal.pone.0013928.g003 we examined L11.3 in our indirect ELISA system. Like OMAB, L11.3 showed a strong selectivity for oligomeric Ab (Fig. 5A). The reaction pattern of human IgM against Ab was further studied by investigating plasma from a group of healthy donors. Similar to both the murine OMAB and the human L11.3 monoclonal antibodies, human plasma IgM bound oligomeric Ab, while Ab monomers and dimers were omitted (Fig. 5B). Discussion Self-assembly of monomeric Ab peptides is a multifactorial process, where the resulting aggregates can differ in both morphology and molecular structure. This difference is reflected in the ability of the different Ab aggregates to exert a pathological effect. Compelling evidence suggests that small, soluble oligomeric species, and not large, insoluble aggregates, are the most cytotoxic Ab species. This hypothesis has been supported by cell-culture viability assays and through numerous animal experiments, where several independent investigations have described memory impair- ment in APP transgenic mice to precede the detection of Ab depositions [32,33,34,35]. Soluble Ab oligomers, heterogeneous assemblies vastly ranging in size, were initially described as a soluble pool of Ab that remained in solution after ultra-centrifugation [36]. This Ab pool was subsequently divided into subfractions from 10 to 100 kDa using filters with different molecular weight cut-offs. To date, a variety of different soluble Ab species have been characterized and their physiological effects characterized (for a recent review, see Shankar et al [37]). Thus, a large accumulation of PLoS ONE | www.plosone.org 5 November 2010 | Volume 5 | Issue 11 | e13928