UseCases_ArguminSci_Discourse  

PubMed:11932745 JSONTXT 6 Projects

Annnotations TAB TSV DIC JSON TextAE Lectin_function IAV-Glycan

Id Subject Object Predicate Lexical cue
T1 0-113 DRI_Background denotes Naturally secreted oligomers of amyloid beta protein potently inhibit hippocampal long-term potentiation in vivo.
T2 114-411 DRI_Background denotes Although extensive data support a central pathogenic role for amyloid beta protein (Abeta) in Alzheimer's disease, the amyloid hypothesis remains controversial, in part because a specific neurotoxic species of Abeta and the nature of its effects on synaptic function have not been defined in vivo.
T3 412-596 DRI_Outcome denotes Here we report that natural oligomers of human Abeta are formed soon after generation of the peptide within specific intracellular vesicles and are subsequently secreted from the cell.
T4 597-790 DRI_Background denotes Cerebral microinjection of cell medium containing these oligomers and abundant Abeta monomers but no amyloid fibrils markedly inhibited hippocampal long-term potentiation (LTP) in rats in vivo.
T5 791-877 DRI_Approach denotes Immunodepletion from the medium of all Abeta species completely abrogated this effect.
T6 878-1023 DRI_Outcome denotes Pretreatment of the medium with insulin-degrading enzyme, which degrades Abeta monomers but not oligomers, did not prevent the inhibition of LTP.
T7 1024-1201 DRI_Challenge denotes Therefore, Abeta oligomers, in the absence of monomers and amyloid fibrils, disrupted synaptic plasticity in vivo at concentrations found in human brain and cerebrospinal fluid.
T8 1202-1401 DRI_Background denotes Finally, treatment of cells with gamma-secretase inhibitors prevented oligomer formation at doses that allowed appreciable monomer production, and such medium no longer disrupted LTP, indicating that
T9 1402-1420 Token_Label.OUTSIDE denotes synaptotoxic Abeta
T10 1421-1463 DRI_Background denotes oligomers can be targeted therapeutically.