title: Neuron Loss and Behavioral Deficits in the TBA42 Mouse Model Expressing N-Truncated Pyroglutamate Amyloid-β3-42.
abstract: Pyroglutamate-modified amyloid-β (Aβ) at amino acid position three (Aβ(pE3-42)) is gaining considerable attention as a potential key player in the pathogenesis of Alzheimer's disease (AD). Aβ(pE3-42) is abundant in AD brain and has a high aggregation propensity, stability, and cellular toxicity. The aim of the present work was to study the effect of Aβ(pE3-42) expression on neuron loss and associated behavioral deficits using the TBA42 transgenic mouse model. Expression of pyroglutamate Aβ(3-42) triggers hippocampal CA1 neuron loss and behavioral deficits in the TBA42 mouse model. Mice elicited significant neuron death (-35% at the age of 12 months), deficits in the spatial reference memory, working memory, loss of anxiety, and severe motor deficits in an age-dependent manner. These results support a major pathological function of pyroglutamate Aβ in AD.
authors.affiliation: Division of Molecular Psychiatry, Department of Psychiatry and Psychotherapy, University Medicine Göttingen, Georg-August-University of Göttingen, Germany.
authors.forename: Julius N
authors.initials: JN
authors.lastname: Meißner
authors.affiliation: Division of Molecular Psychiatry, Department of Psychiatry and Psychotherapy, University Medicine Göttingen, Georg-August-University of Göttingen, Germany.
authors.forename: Yvonne
authors.initials: Y
authors.lastname: Bouter
authors.affiliation: Division of Molecular Psychiatry, Department of Psychiatry and Psychotherapy, University Medicine Göttingen, Georg-August-University of Göttingen, Germany.
authors.forename: Thomas A
authors.initials: TA
authors.lastname: Bayer
mesh_terms: D000367:Age Factors; D000544:Alzheimer Disease / Q000150:complications / Q000235:genetics / Q000473:pathology; D016229:Amyloid beta-Peptides / Q000235:genetics*; D000818:Animals; D056547:CA1 Region, Hippocampal / Q000473:pathology*; D016923:Cell Death / Q000235:genetics; D004195:Disease Models, Animal; D006801:Humans; D018782:Maze Learning / Q000502:physiology; D001523:Mental Disorders / Q000209:etiology*; D051379:Mice; D008822:Mice, Transgenic; D009069:Movement Disorders / Q000209:etiology; D053580:Muscle Strength / Q000235:genetics; D009474:Neurons / Q000473:pathology*; D010446:Peptide Fragments / Q000235:genetics*; D011597:Psychomotor Performance / Q000502:physiology; D065853:Spatial Learning / Q000502:physiology
chemical_list: D016229:Amyloid beta-Peptides; D010446:Peptide Fragments; C532271:amyloid beta-protein (3-42), pyroglutamyl(3)-
keywords: Hippocampus; N-truncated Aβ; motor deficits; spatial reference memory; stereology; transgenic mouse model; working memory