Epitopes described in "Reversible memory loss in a mouse transgenic model of Alzheimer's disease."

Article Authors:Linda A Kotilinek; Brian Bacskai; Marcus Westerman; Takeshi Kawarabayashi; Linda Younkin; Bradley T Hyman; Steven Younkin; Karen H Ashe
Article Title:Reversible memory loss in a mouse transgenic model of Alzheimer's disease.
Reference Detail
Reference ID:1014403
Abstract:Alzheimer's disease (AD) is a neurodegenerative condition, believed to be irreversible, characterized by inexorable deterioration of memory and intellect, with neuronal loss accompanying amyloid plaques and neurofibrillary tangles. In an amyloid precursor protein transgenic mouse model, Tg2576, little or no neuronal loss accompanies age-related memory impairment or the accumulation of Abeta, a 40-42 aa polypeptide found in plaques. Recently, we have shown inverse correlations between brain Abeta and memory in Tg2576 mice stratified by age (Westerman et al., 2002). Broadening the age range examined obscured this relationship, leading us to propose that small, soluble assemblies of Abeta disrupt cognitive function in these mice. Here we show that memory loss can be fully reversed in Tg2576 mice using intraperitoneally administered BAM-10, a monoclonal antibody recognizing the N terminus of Abeta. The beneficial effect of BAM-10 was not associated with a significant Abeta reduction, but instead eliminated the inverse relationship between brain Abeta and memory. We postulate that BAM-10 acts by neutralizing Abeta assemblies in the brain that impair cognitive function. Our results indicate that a substantial portion of memory loss in Tg2576 mice is not permanent. If these Abeta assemblies contribute significantly to memory loss in AD, then successfully targeting them might improve memory in some AD patients.
Affiliations:Department of Neurology, University of Minnesota, Minneapolis 55455, USA.
Reference Type:Literature
PubMed ID:12151510
Journal:J Neurosci
Journal Volume:22
Article Pages:6331-5
Journal ISSN:1529-2401
Article Chemical List:Amyloid beta-Peptides;Amyloid beta-Protein Precursor;Antibodies, Monoclonal
Article MeSH List:Aging(metabolism); Alzheimer Disease(complications; physiopathology); Amyloid beta-Peptides(analysis; antagonists & inhibitors; metabolism); Amyloid beta-Protein Precursor(genetics); Animals; Antibodies, Monoclonal(pharmacology); Behavior, Animal(drug effects); Brain Chemistry; Cognition(drug effects); Disease Models, Animal; Female; Immunization, Passive(methods); Injections, Intraperitoneal; Male; Memory(drug effects); Memory Disorders(complications; drug therapy; physiopathology); Mice; Mice, Transgenic; Remission Induction(methods); Spatial Behavior(drug effects)
Curation Last Updated:2014-10-03 21:29:55