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摘要
Though phase I clinical trial of immunotherapy for Alzheimer's disease(AD) with inoculated A beta 42 in humans had been proven to be effective, phase II immunotherapy trial was discontinued in 2002 because a few patients developed significant inflammatory reactions caused by C-terminal domain of A beta 42. The aim of the study was to investigate the levels and the abilities of antibodies induced by C-terminal truncated A beta species to inhibit A beta 42 aggregation and cytotoxity in vitro. 46-week-old male BALB/c mice, A beta 42 and A beta 28/A beta 35/A beta 42 with a C-terminal eight-histidine tag(A beta 28H8, A beta 35H8, and A beta 42H8) were applied in the present study. The mice were randomly divided into 5 groups(n=8), control mice immunized with the normal saline, A beta 42-immunized mice and A beta 42H-/A beta 35H-/A beta 28H-immunized mice. All the serum antibodies were evaluated by measuring their abilities to inhibit A beta 42 aggregation and cytotoxity in vitro. Each mouse was vaccinated with purified A beta peptide emulsified with Freund's adjuvant(volume ratio 1:1). Titers, concentrations and isotypes of serum antibodies against A beta 42 were measured by indirect ELISA. Effects of serum antibodies on A beta 42 aggregation and disassembly of A beta 42 fibrils in vitro were observed by electron microscopy. Effects of serum antibodies on A beta 42 cytotoxicity were determined by MTT assay. A beta 42 or A beta 28 could induce higher anti-A beta 42 antibody titer(1:6400) than A beta 35(1:3200). Significantly, A beta 28 induced more IgG1 and IgG2b isotype antibodies and less IgG2b isotype antibody than other A beta species though all the induced serum antibodies could inhibit A beta 42 aggregation or fibrillogenesis, could induce the disassembly of A beta 42 aggregates, and neutralized or inhibited the cytotoxicity of A beta 42 in vitro. C-Terminal truncated A beta 28 could induce the same effective but safer serum antibodies against A beta 42 than full length A beta 42 by eliciting more Th2-type immune responses.
- 出版日期2010-11
- 单位吉林大学
