Alzheimer's disease immunotherapy: From in vitro amyloid immunomodulation to in vivo vaccination

摘要: Site-directed antibodies which modulate conformation of amyloid-beta peptide (Abeta) became the theoretical basis immunological approach for treatment Alzheimer's disease (AD). Indeed, towards EFRH sequence, located between amino acids 3-6 N-terminal region Abeta, found to be a key position in modulation Abeta conformation, prevent formation fibrillar and dissolve already formed amyloid plaques. The performance anti-Abeta transgenic mice models AD showed they are delivered central nervous system (CNS), preventing and/or dissolving Abeta. Moreover, these protected from learning age-related memory deficits. Development such via active passive immunization against fragments has been proposed immunotherapeutic strategies. Experimental with 1-42 hu-mans was stopped phase II clinical trials due unexpected neuroinflammatory manifestations. In spite fact that it will take considerable effort establish suitable procedure, results clearly strengthen hypothesis plays role AD, stimulating new area development immunotherapeutics.