Evidence supporting a role for anti-Abeta antibodies in the treatment of Alzheimer's disease.
Antibodies against Abeta have been suggested as potential therapeutic strategies for the treatment of Alzheimer disease (AD) for nearly 8 years. Animal studies have been very encouraging in that both active and passive immunization of transgenic mice can reduce amyloid load and reverse memory deficits found in these mice. Three mechanisms have been proposed to explain these results: (a). catalytic conversion of fibrillar Abeta to less toxic forms, (b). opsonization of Abeta deposits leading to microglial phagocytosis, or (c). promote the efflux of Abeta from the brain to the circulation. Evidence exists supporting all three mechanisms, which, it should be noted, are not mutually exclusive. Phase 2 clinical trials of active immunization with vaccines against human Abeta1-42 were halted due to an unacceptable incidence of meningoencephalitic reactions (6% of patients treated). However, a recent report from a fraction of the patients in this trial found that those patients developing antibodies which reacted with brain amyloid deposits had a significantly slower progression of cognitive loss over a period of 12 months. This supports the continued cautious testing of passive immunization and, possibly even active immunization against the Abeta peptide using preparations less likely to cause autoimmune reactions in the central nervous system.
Morgan
Dave
D
Department of Pharmacology, University of South Florida, 12901 Downs Blvd, MDC Box 9, Tampa, FL 33612-4799, USA. dmorgan@hsc.usf.edu
Gitter
Bruce D
BD
D000544:Alzheimer Disease / Q000628:therapy*; D023582:Alzheimer Vaccines / Q000627:therapeutic use*; D016229:Amyloid beta-Peptides / Q000276:immunology*; D000818:Animals; D000906:Antibodies / Q000627:therapeutic use; D019317:Evidence-Based Medicine / Q000379:methods; D006801:Humans; D007114:Immunization / Q000379:methods; D007167:Immunotherapy / Q000379:methods*; D051379:Mice
D023582:Alzheimer Vaccines; D016229:Amyloid beta-Peptides; D000906:Antibodies