title: Paired helical filament-like phosphorylation of tau, deposition of beta/A4-amyloid and memory impairment in rat induced by chronic inhibition of phosphatase 1 and 2A.
abstract: Alzheimer's disease is histopathologically characterized by neurofibrillary tangles, formed by the abnormally high phosphorylated tau protein, and senile plaques which largely consist of the beta/A4-amyloid peptide. Metabolism of the amyloid precursor protein and its processing into beta/A4-amyloid is regulated by protein phosphorylation. Thus, an imbalance between protein phosphorylation and dephosphorylation might be crucial for the development of the molecular hallmarks of Alzheimer's disease. We report here that chronic infusion into rat brain ventricles of okadaic acid, a specific inhibitor of the serine/threonine protein phosphatases 1 and 2A, results in a severe memory impairment, accompanied by a paired helical filament-like phosphorylation of tau protein and the formation of beta/A4-amyloid containing plaque-like structures in gray and white matter areas.
authors.affiliation: Paul Flechsig Institute of Brain Research, Department of Neurochemistry, University of Leipzig, Germany.
authors.forename: T
authors.initials: T
authors.lastname: Arendt
authors.forename: M
authors.initials: M
authors.lastname: Holzer
authors.forename: R
authors.initials: R
authors.lastname: Fruth
authors.forename: M K
authors.initials: MK
authors.lastname: Brückner
authors.forename: U
authors.initials: U
authors.lastname: Gärtner
mesh_terms: D016229:Amyloid beta-Peptides / Q000378:metabolism*; D000818:Animals; D001921:Brain / Q000378:metabolism*; D004988:Ethers, Cyclic / Q000494:pharmacology*; D005260:Female; D007276:Injections, Intraventricular; D008569:Memory Disorders / Q000139:chemically induced*; D019319:Okadaic Acid; D010744:Phosphoric Monoester Hydrolases / Q000037:antagonists & inhibitors*; D010766:Phosphorylation; D051381:Rats; D017208:Rats, Wistar; D013997:Time Factors; D016875:tau Proteins / Q000378:metabolism*
chemical_list: D016229:Amyloid beta-Peptides; D004988:Ethers, Cyclic; D016875:tau Proteins; D019319:Okadaic Acid; D010744:Phosphoric Monoester Hydrolases