title: Immunotherapy for Alzheimer's disease.
abstract: A primary goal of research on Alzheimer's disease is to develop disease modifying therapeutics. The amyloid cascade hypothesis has focused the initial efforts on methods to reduce amyloid. One surprising approach that has shown considerable success in mouse models and has hinted at benefits in human trials is anti-Abeta immunotherapy. Schenk first showed the amyloid reducing potential of active immunization in 1999. This prompted our group and that of St. George-Hyslop to investigate whether active immunization would similarly retard the memory deficits that develop in amyloid depositing transgenic mice. Contrary to our initial predictions of premature memory dysfunction due to inflammation, vaccination protected amyloid depositing mice from developing memory deficits. Subsequent studies found that passive immunization could reverse memory deficits, even when administered for short periods. These encouraging findings led to a trial of an Abeta vaccination in Alzheimer patients. The trial was cut short due to meningoencephalitic symptoms in 6% of patients, yet, in a subset of patients, those developing brain reactive antibodies benefited from slower rates of cognitive decline. These observations have accelerated the development of passive immunization protocols and safer vaccines. At this time, anti-amyloid immunotherapy stands poised to be the first test of the amyloid hypothesis in the treatment of Alzheimer disease.
authors.affiliation: Alzheimer Research Laboratory, Department of Pharmacology and Molecular Therapeutics, University of South Florida, Tampa, FL 33612, USA. dmorgan@hsc.usf.edu
authors.forename: Dave
authors.initials: D
authors.lastname: Morgan
mesh_terms: D000544:Alzheimer Disease / Q000378:metabolism / Q000628:therapy*; D016564:Amyloid beta-Protein Precursor / Q000378:metabolism; D006801:Humans; D007167:Immunotherapy / Q000379:methods*; D016233:Immunotherapy, Active / Q000379:methods*; D014611:Vaccination / Q000379:methods
chemical_list: D016564:Amyloid beta-Protein Precursor