title: Epitope mapping of antibodies against TDP-43 and detection of protease-resistant fragments of pathological TDP-43 in amyotrophic lateral sclerosis and frontotemporal lobar degeneration.
abstract: TAR DNA-binding protein of 43 kDa (TDP-43) is the major component of the intracellular inclusions in amyotrophic lateral sclerosis (ALS) and frontotemporal lobar degeneration (FTLD). Here, we show that both monoclonal (60019-2-Ig) and polyclonal (10782-2-AP) anti-TDP-43 antibodies recognize amino acids 203-209 of human TDP-43. The monoclonal antibody labeled human TDP-43 by recognizing Glu204, Asp205 and Arg208, but failed to react with mouse TDP-43. The antibodies stained the abnormally phosphorylated C-terminal fragments of 24-26 kDa in addition to normal TDP-43 in ALS and FTLD brains. Immunoblot analysis after protease treatment demonstrated that the epitope of the antibodies (residues 203-209) constitutes part of the protease-resistant domain of TDP-43 aggregates which determine a common characteristic of the pathological TDP-43 in both ALS and FTLD-TDP. The antibodies and methods used in this study will be useful for the characterization of abnormal TDP-43 in human materials, as well as in vitro and animal models for TDP-43 proteinopathies.
authors: Department of Neuropathology and Cell Biology, Tokyo Metropolitan Institute of Medical Science, Tokyo, Japan.
authors: Hiroshi
authors: H
authors: Tsuji
authors: Takashi
authors: T
authors: Nonaka
authors: Makiko
authors: M
authors: Yamashita
authors: Masami
authors: M
authors: Masuda-Suzukake
authors: Fuyuki
authors: F
authors: Kametani
authors: Haruhiko
authors: H
authors: Akiyama
authors: David M A
authors: DM
authors: Mann
authors: Akira
authors: A
authors: Tamaoka
authors: Masato
authors: M
authors: Hasegawa
mesh_terms: D000595:Amino Acid Sequence; D000690:Amyotrophic Lateral Sclerosis / Q000378:metabolism*; D000818:Animals; D000906:Antibodies / Q000737:chemistry / Q000276:immunology*; D000911:Antibodies, Monoclonal / Q000737:chemistry / Q000276:immunology; D001921:Brain / Q000276:immunology / Q000378:metabolism; D001923:Brain Chemistry; D004268:DNA-Binding Proteins / Q000737:chemistry / Q000276:immunology* / Q000378:metabolism; D018604:Epitope Mapping; D057174:Frontotemporal Lobar Degeneration / Q000378:metabolism*; D006801:Humans; D051379:Mice; D008969:Molecular Sequence Data; D010447:Peptide Hydrolases / Q000737:chemistry
chemical_list: D000906:Antibodies; D000911:Antibodies, Monoclonal; D004268:DNA-Binding Proteins; D010447:Peptide Hydrolases