Alz-50 and MC-1, a new monoclonal antibody raised to paired helical filaments, recognize conformational epitopes on recombinant tau.
Using a series of recombinant tau and FAC1 mutant proteins, this study demonstrates by Western and dot blot analysis that 1) shared epitopes between tau and FAC1 are responsible for Alz-50 binding; 2) Alz-50 reactivity is dependent on two discontinuous portions of the tau molecule; 3) Alz-50 reactivity is most likely the result of a conformational alteration of tau monomers in Alzheimer's disease; and 4) the epitope for MC-1, a novel monoclonal antibody, maps to similar regions of tau but does not react with FAC1. These data raise questions regarding previous studies which have suggested that tau lacks a specific conformation and illustrate the utility of the Alz-50 and MC-1 antibodies in recognizing a distinct pathological conformation of the tau molecule in Alzheimer's disease.
Jicha
G A
GA
Department of Pathology, Albert Einstein College of Medicine, Bronx, New York 10461, USA.
Bowser
R
R
Kazam
I G
IG
Davies
P
P
D000911:Antibodies, Monoclonal; D000937:Antigen-Antibody Reactions; D000941:Antigens / Q000032:analysis / Q000276:immunology*; D034961:Antigens, Nuclear; D018604:Epitope Mapping; D000939:Epitopes / Q000276:immunology*; D006801:Humans; D016297:Mutagenesis, Site-Directed; D009419:Nerve Tissue Proteins / Q000737:chemistry / Q000235:genetics / Q000276:immunology; D016874:Neurofibrillary Tangles / Q000737:chemistry / Q000276:immunology*; D011487:Protein Conformation; D011994:Recombinant Proteins / Q000276:immunology; D014157:Transcription Factors; D016875:tau Proteins / Q000737:chemistry / Q000235:genetics / Q000276:immunology*; D000092468:Bromodomain Containing Proteins
D000911:Antibodies, Monoclonal; D000941:Antigens; D034961:Antigens, Nuclear; D000939:Epitopes; D009419:Nerve Tissue Proteins; D011994:Recombinant Proteins; D014157:Transcription Factors; D016875:tau Proteins; C056167:Alzheimer's disease antigen; C406238:fetal Alzheimer antigen; D000092468:Bromodomain Containing Proteins