SAGE KE Bulletin Board
Development of anti A-beta oligomeric antibodies, the next stage in the anti A-beta immunotherapy
16 December 2005
Immunization with anti amyloid beta (A-beta) antibodies reduces A- beta deposition and improves cognitive function (Schenk et al., 1999) but encephalitis (Senior, 2002; Nicoll et al., 2003) and haemorrhage have been seen as side effects of A-beta immunization (Pfeifer et al., 2002; Racke et al., 2005).
To avoid these side effects new immunization strategies are in development. Several studies with immunogens against the truncated A-beta 1-15 peptide that contains the B cell epitope but lacks T cell reactive site of full length A-beta 1-42 and antibodies against A-beta oligomers were presented at the 34th SfN Annual Meeting 2005. Immunization with these compounds lead to behavioural improvement in APP transgenic mice (Maier et al. (2005); Jiang et al. (2005)). Lemere et al. also developed a dendrimeric A-beta 1-15 vaccine that administrated together with adjuvant LT(R192G) reduced plaque deposition, gliosis and neuritic dystrophies. Ma et al. showed that immunization with anti A-beta antibodies directed against oligomerimers of A-beta 1-15 reduced several different oligomeric forms of A-beta but not insoluble forms in Tg2576 transgenic mice. The reduction of A-beta correlated significantly with that of GSK-3-beta activity, a major tau kinase. These results were confirmed with an antibody that recognized oligomeric A-beta but does not recognized monomer or plaque amyloid. Reduction of phosphorilated tau after A-beta immunization strongly indicates that A-beta may lead the tangle formation and that specific anti A-beta oligomeric antibodies become very important in the development of the therapy. In summary, the development of antibodies avoiding T-cell activation may be an important step in establishing the appropriate tools for successful anti A-beta immunotherapy for AD pathology. Anti A-beta oligomeric antibodies, thereby, seem to be ideally suited to fulfil these criteria since they do not react with monomeric forms of A-beta.
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- C.A.Lemere, M.Maier, L.Jiang, G.Bitan, T.J.Seabrook. Dendrimeric A 1 - 15 intranasal immunization attenuates cerebral A while avoiding an A - specific cellular immune response in J20 APP transgenic mice. Program No. 703.7. 2005 Abstract Viewer/Itinerary Planner. Washington, DC: Society for Neuroscience.
- Nicoll JA, Wilkinson D, Holmes C, Steart P, Markham H, Weller RO (2003) Neuropathology of human Alzheimer disease after immunization with amyloid-beta peptide: a case report. Nat Med 9:448-452.
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