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Neurofilament Monoclonal Antibodies RT97 and 8D8 Recognize Different Modified Epitopes in Paired Helical Filament‐τ in Alzheimer's Disease
Author(s) -
Brion JeanPierre,
Couck AnneMarie,
Robertson Janice,
Loviny Thérèse L. F.,
Anderton Brian H.
Publication year - 1993
Publication title -
journal of neurochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.75
H-Index - 229
eISSN - 1471-4159
pISSN - 0022-3042
DOI - 10.1111/j.1471-4159.1993.tb03298.x
Subject(s) - epitope , neurofilament , chemistry , monoclonal antibody , antibody , microbiology and biotechnology , gene isoform , alzheimer's disease , amino acid , biochemistry , immunohistochemistry , pathology , biology , immunology , disease , medicine , gene
Neurofibrillary tangles in Alzheimer's disease have been previously found to be labeled by some neurofilament antibodies that also recognize τ proteins. We have studied the reactivity of two such monoclonal antibodies, RT97 and 8D8, and of an anti‐ubiquitin serum with the abnormal paired helical filaments (PHF)‐τ (A68) polypeptides known to be the main component of the PHFs constituting the neurofibrillary tangles. 8D8 recognized the three major PHF‐τ polypeptides, but RT97 reacted only with the two larger PHF‐τ species. PHF‐τ polypeptides were labeled by 8D8 and RT97 much more strongly than normal human τ and this labeling was decreased after alkaline phosphatase treatment. Anti‐ubiquitin and anti‐phosphotyrosine antibodies did not label PHF‐τ polypeptides. The immunoreactivity of proteolytic fragments of PHF‐τ polypeptides was studied with RT97, 8D8, and a panel of τ antibodies. The epitope for 8D8 on PHF‐τ was localized between amino acids 222 and 427 in the carboxyl half of τ. The RT97 epitope on PHF‐τ was localized in the amino domain of τ, probably in the 29‐amino‐acid insertion (insert 1) found towards the amino terminus of some τ isoforms. These results show that the basis for the labeling of neurofibrillary tangles by antibodies 8D8 and RT97 to neurofilament is their ability to react with PHF‐τ polypeptides by recognizing sites specifically modified on PHF‐τ, including a site specific to some τ isoforms.