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- W2085304612 abstract "Alzheimer's disease is the most common of the conformational neurodegenerative disorders, where the pathogenesis is linked to a normal protein undergoing a shape change into a pathological conformer with a high β-sheet content. In the case of AD this involves both amyloid β and abnormally phosphorylated tau forming toxic oligomeric structures, as well as neuritic plaques, congophilic angiopathy and neurofibrillary tangles. In the case of another conformational disorder, the prion diseases, the pathogenesis is linked to a change in the cellular prion protein (PrPC) into the disease associated PrPSc. Despite their biochemical heterogeneity the pathological conformers underlying the pathogenesis of the various conformational disorders show pathological conformation mimicry. We sought to develop monoclonal antibodies which would recognize this shared pathological conformation. We immunized mice with aggregated British amyloid (ABri) related peptides in a predominantly β-sheet conformation alone or in combination with related immunogens. ABri is a rare form of familial human amyloidosis associated with a mis-sense mutation in a stop codon resulting in the production of a highly amyloidogenic protein with no sequence homology to other native human proteins. Spleens from these immunized mice, as well as from mice with a “successful” response to vaccination from our other AD and prion vaccination experiments were used for hybridoma production with clones screened for immunoreactivity to various amyloid peptides/proteins such as Aβ42, purified neurofibrillary tangles and PrPSc. Our immunization protocol produced a number of monoclonal antibodies (Mabs) which recognize multiple amyloid proteins by ELISA, Western blot and tissue immunolabeling which have no sequence homology. We report the production of several novel conformational monoclonal antibodies that recognize several disease associated peptides/proteins that show pathological conformational mimicry. Such Mabs have potential use for diagnostic and therapeutic purposes." @default.
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- W2085304612 date "2010-07-01" @default.
- W2085304612 modified "2023-10-06" @default.
- W2085304612 title "P3-463: Development of conformational monoclonal antibodies that detects multiple amyloid proteins" @default.
- W2085304612 doi "https://doi.org/10.1016/j.jalz.2010.05.2006" @default.
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