title: Naturally occurring autoantibodies against beta-amyloid: investigating their role in transgenic animal and in vitro models of Alzheimer's disease.
abstract: Alzheimer's disease (AD) is a neurodegenerative disorder primarily affecting regions of the brain responsible for higher cognitive functions. Immunization against β-amyloid (Aβ) in animal models of AD has been shown to be effective on the molecular level but also on the behavioral level. Recently, we reported naturally occurring autoantibodies against Aβ (NAbs-Aβ) being reduced in Alzheimer's disease patients. Here, we further investigated their physiological role: in epitope mapping studies, NAbs-Aβ recognized the mid-/C-terminal end of Aβ and preferentially bound to oligomers but failed to bind to monomers/fibrils. NAbs-Aβ were able to interfere with Aβ peptide toxicity, but NAbs-Aβ did not readily clear senile plaques although early fleecy-like plaques were reduced. Administration of NAbs-Aβ in transgenic mice improved the object location memory significantly, almost reaching performance levels of wild-type control mice. These findings suggest a novel physiological mechanism involving NAbs-Aβ to dispose of proteins or peptides that are prone to forming toxic aggregates.
authors.affiliation: Department of Neurology, Philipps University Marburg, D-35043 Marburg, Germany. dodel@med.uni-marburg.de
authors.forename: Richard
authors.initials: R
authors.lastname: Dodel
authors.forename: Karthikeyan
authors.initials: K
authors.lastname: Balakrishnan
authors.forename: Kathy
authors.initials: K
authors.lastname: Keyvani
authors.forename: Oliver
authors.initials: O
authors.lastname: Deuster
authors.forename: Frauke
authors.initials: F
authors.lastname: Neff
authors.forename: Luminita-Cornelia
authors.initials: LC
authors.lastname: Andrei-Selmer
authors.forename: Stephan
authors.initials: S
authors.lastname: Röskam
authors.forename: Carsten
authors.initials: C
authors.lastname: Stüer
authors.forename: Yousef
authors.initials: Y
authors.lastname: Al-Abed
authors.forename: Carmen
authors.initials: C
authors.lastname: Noelker
authors.forename: Monika
authors.initials: M
authors.lastname: Balzer-Geldsetzer
authors.forename: Wolfgang
authors.initials: W
authors.lastname: Oertel
authors.forename: Yansheng
authors.initials: Y
authors.lastname: Du
authors.forename: Michael
authors.initials: M
authors.lastname: Bacher
mesh_terms: D000544:Alzheimer Disease / Q000235:genetics* / Q000276:immunology* / Q000473:pathology / Q000523:psychology; D016229:Amyloid beta-Peptides / Q000276:immunology*; D000818:Animals; D030801:Animals, Genetically Modified; D000917:Antibody Formation; D001323:Autoantibodies / Q000276:immunology*; D001522:Behavior, Animal; D001921:Brain / Q000473:pathology; D002478:Cells, Cultured; D002850:Chromatography, Gel; D004195:Disease Models, Animal; D000939:Epitopes; D005260:Female; D006801:Humans; D007114:Immunization; D007074:Immunoglobulin G / Q000276:immunology; D007150:Immunohistochemistry; D051379:Mice; D008810:Mice, Inbred C57BL; D008958:Models, Molecular; D058225:Plaque, Amyloid / Q000473:pathology; D020349:Surface Plasmon Resonance
chemical_list: D016229:Amyloid beta-Peptides; D001323:Autoantibodies; D000939:Epitopes; D007074:Immunoglobulin G