title: Internalized antibodies to the Abeta domain of APP reduce neuronal Abeta and protect against synaptic alterations.
abstract: Immunotherapy against beta-amyloid peptide (Abeta) is a leading therapeutic direction for Alzheimer disease (AD). Experimental studies in transgenic mouse models of AD have demonstrated that Abeta immunization reduces Abeta plaque pathology and improves cognitive function. However, the biological mechanisms by which Abeta antibodies reduce amyloid accumulation in the brain remain unclear. We provide evidence that treatment of AD mutant neuroblastoma cells or primary neurons with Abeta antibodies decreases levels of intracellular Abeta. Antibody-mediated reduction in cellular Abeta appears to require that the antibody binds to the extracellular Abeta domain of the amyloid precursor protein (APP) and be internalized. In addition, treatment with Abeta antibodies protects against synaptic alterations that occur in APP mutant neurons.
authors.affiliation: Department of Neurology and Neuroscience, Weill Medical College of Cornell University, New York, New York 10021, USA.
authors.forename: Davide
authors.initials: D
authors.lastname: Tampellini
authors.forename: Jordi
authors.initials: J
authors.lastname: Magrané
authors.forename: Reisuke H
authors.initials: RH
authors.lastname: Takahashi
authors.forename: Feng
authors.initials: F
authors.lastname: Li
authors.forename: Michael T
authors.initials: MT
authors.lastname: Lin
authors.forename: Cláudia G
authors.initials: CG
authors.lastname: Almeida
authors.forename: Gunnar K
authors.initials: GK
authors.lastname: Gouras
mesh_terms: D000544:Alzheimer Disease / Q000276:immunology / Q000628:therapy*; D053829:Amyloid Precursor Protein Secretases / Q000378:metabolism; D016564:Amyloid beta-Protein Precursor / Q000737:chemistry / Q000276:immunology* / Q000378:metabolism; D000818:Animals; D000911:Antibodies, Monoclonal / Q000493:pharmacokinetics*; D000918:Antibody Specificity; D000936:Antigen-Antibody Complex / Q000378:metabolism; D045744:Cell Line, Tumor; D004705:Endocytosis; D007114:Immunization / Q000379:methods; D051379:Mice; D008822:Mice, Transgenic; D009447:Neuroblastoma; D009474:Neurons / Q000473:pathology*; D017434:Protein Structure, Tertiary; D013569:Synapses / Q000473:pathology*; D013696:Temperature
chemical_list: D016564:Amyloid beta-Protein Precursor; D000911:Antibodies, Monoclonal; D000936:Antigen-Antibody Complex; D053829:Amyloid Precursor Protein Secretases