Conformationally abnormal forms of tau proteins and specific antibodies thereto

Abstract

The invention relates to antibodies with a specificity to an abnormally truncated form of tau protein, which is conformationally different from normal tau, and does not bind to normal tau protein, conformationally different tau proteins (“tauons”) and diagnostic and therapeutical aspects in relation to Alzheimer's disease and related tauopathies.

1 . An isolated antibody that:
 (a) specifically recognizes an epitope in the amino acid sequence of SEQ ID NO: 1 of a truncated form of human tau protein that comprises the amino acid sequence of SEQ ID NO: 1 and consists of between 100 to 400 amino acid residues of the human tau protein, the truncated form of the human tau protein being conformationally different from normal human tau protein; and   (b) does not specifically recognize normal human tau protein.   
     
     
         2 . The antibody of  claim 1 , wherein the truncated form of human tau protein is truncated at the N-terminus. 
     
     
         3 . The antibody of  claim 1 , wherein the truncated form of human tau protein is truncated at the C-terminus. 
     
     
         4 . The antibody of  claim 1 , wherein the truncated form of human tau protein is truncated at both termini. 
     
     
         5 . A hybridoma cell line producing an antibody that:
 (a) specifically recognizes an epitope in the amino acid sequence of SEQ ID NO: 1 of a truncated form of human tau protein that comprises the amino acid sequence of SEQ ID NO: 1 and consists of between 100 to 400 amino acid residues of the human tau protein, the truncated form of the human tau protein being conformationally different from normal human tau protein; and   (b) does not specifically recognize normal human tau protein.   
     
     
         6 . A method for detecting truncated forms of human tau protein comprising:
 (a) mixing a sample of brain tissue or cerebral spinal fluid with an antibody that: (i) specifically recognizes an epitope in the amino acid sequence of SEQ ID NO: 1 of a truncated form of human tau protein that comprises the amino acid sequence of SEQ ID NO: 1 and consists of between 100 to 400 amino acid residues of the human tau protein, the truncated form of the human tau protein being conformationally different from normal human tau protein; and (ii) does not specifically recognize normal human tau protein; and   (b) detecting a binding event between said antibody and the truncated form of human tau protein, wherein detecting the binding event detects the truncated forms of human tau protein in the sample.   
     
     
         7 . The method of  claim 6 , wherein detecting the binding event comprises using a secondary antibody. 
     
     
         8 . The method of  claim 7 , wherein the secondary antibody is labeled. 
     
     
         9 . The method of  claim 6 , further comprising quantifying the amount of the truncated form of human tau protein bound to the antibody. 
     
     
         10 . The method of  claim 9 , wherein quantifying the truncated forms of human tau protein comprises using a standard preparation of the truncated form of human tau protein. 
     
     
         11 . A method of inhibiting neuron degeneration comprising administering to a neuron an antibody that: (i) specifically recognizes an epitope in the amino acid sequence of SEQ ID NO: 1 of a truncated form of human tau protein that comprises the amino acid sequence of SEQ ID NO: 1 and consists of between 100 to 400 amino acid residues of the human tau protein, the truncated form of the human tau protein being conformationally different from normal human tau protein; and (ii) does not specifically recognize normal human tau protein, wherein degeneration of the neuron degeneration is inhibited. 
     
     
         12 . The method of  claim 11 , wherein the antibody is an isolated DC-11 antibody as produced by hybridoma cell line DC-11 (ECACC Deposit No: 00082215). 
     
     
         13 . The method of  claim 11 , wherein the antibody is an isolated DC-11/I antibody as produced by hybridoma cell line DC-11/I (ECACC Deposit No: 00082216).