Immunological approach for the treatment of Alzheimer's disease.
Formation of amyloid beta (Abeta) is a complex kinetic and thermodynamic process, dependent on peptidepeptide interactions that may be modulated by other proteins. We found that site-directed antibodies toward peptide (glutamic acid, phenyl alanine, arginine, histidine) EFRH sequences 3-6 of the N-terminal region of beta-amyloid peptide (AbetaP) suppress in vitro formation of Abeta and dissolve already formed fibrillar amyloid. These so-called chaperone-like properties of monoclonal antibodies led to the development of a new immunological approach toward Alzheimer's disease (AD) treatment. Production and performance of anti-Abeta antibodies into the transgenic mouse model of AD showed that these antibodies may be delivered from the periphery to the central nervous system, preventing the formation of Abeta and dissolving amyloid plaques. Moreover, immunization with Abeta protects transgenic mice from the learning and age-related memory deficits that occur in AD. These data support the hypotheses that AbetaP plays a central role in AD, and site-directed antibodies that modulate AbetaP conformation might lead toward immunotherapy of the disease.
D000544:Alzheimer Disease / Q000188:drug therapy* / Q000276:immunology; D016229:Amyloid beta-Peptides / Q000037:antagonists & inhibitors* / Q000276:immunology / Q000494:pharmacology; D000818:Animals; D000911:Antibodies, Monoclonal / Q000276:immunology / Q000627:therapeutic use*; D000918:Antibody Specificity / Q000187:drug effects / Q000276:immunology; D001921:Brain / Q000187:drug effects* / Q000276:immunology; D004195:Disease Models, Animal; D000939:Epitopes / Q000276:immunology; D008569:Memory Disorders / Q000188:drug therapy / Q000276:immunology; D051379:Mice; D008822:Mice, Transgenic; D010446:Peptide Fragments / Q000187:drug effects / Q000276:immunology; D058225:Plaque, Amyloid / Q000187:drug effects / Q000276:immunology; D017434:Protein Structure, Tertiary / Q000187:drug effects / Q000502:physiology
D016229:Amyloid beta-Peptides; D000911:Antibodies, Monoclonal; D000939:Epitopes; D010446:Peptide Fragments