title: Injections of okadaic acid, but not beta-amyloid peptide, induce Alz-50 immunoreactive dystrophic neurites in the cerebral cortex of sheep.
abstract: In an attempt to produce an animal model of neurofibrillary degeneration of the Alzheimer type, okadaic acid (a phosphatase inhibitor) and beta-amyloid peptide (1-40) were microinjected into the cerebral cortex of six adult sheep. After survivals varying from 1 day to 3 months, the injection sites and adjacent areas were evaluated using light microscopic immunocytochemistry. Near sites of implantation of crystalline okadaic acid, the Alz-50 monoclonal antibody stained twisted, dystrophic neurites. None of the beta-amyloid peptide injections caused neurofibrillary pathology. However, immunohistochemical analysis revealed no detectable beta-amyloid peptide remaining in the neuropil, even at 1 day, indicating rapid clearance of the beta-amyloid peptide. The induction of Alz-50 immunoreactive dystrophic neurites by okadaic acid in sheep represents a novel animal model of Alzheimer's neurofibrillary pathology.
authors.affiliation: Committee on Neurobiology, University of Chicago, IL 60637, USA.
authors.forename: P T
authors.initials: PT
authors.lastname: Nelson
authors.forename: C B
authors.initials: CB
authors.lastname: Saper
mesh_terms: D016229:Amyloid beta-Peptides / Q000494:pharmacology*; D000818:Animals; D000911:Antibodies, Monoclonal; D000941:Antigens / Q000032:analysis / Q000276:immunology / Q000378:metabolism*; D002540:Cerebral Cortex / Q000166:cytology; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D005260:Female; D009419:Nerve Tissue Proteins / Q000032:analysis / Q000276:immunology; D016501:Neurites / Q000737:chemistry / Q000201:enzymology / Q000276:immunology*; D016874:Neurofibrillary Tangles / Q000737:chemistry / Q000187:drug effects; D019319:Okadaic Acid / Q000494:pharmacology*; D010744:Phosphoric Monoester Hydrolases / Q000037:antagonists & inhibitors; D012756:Sheep
chemical_list: C056167:Alzheimer's disease antigen; D016229:Amyloid beta-Peptides; D000911:Antibodies, Monoclonal; D000941:Antigens; D004791:Enzyme Inhibitors; D009419:Nerve Tissue Proteins; D019319:Okadaic Acid; D010744:Phosphoric Monoester Hydrolases