Treatment of tauopathies

Abstract

The invention is directed to methods of treatment of Alzheimer's disease and other tauopathies, via the administration of antibodies having specificity to abnormal forms of tau protein, the antibodies showing no binding and/or reactivity to a normal tau protein and being administered under conditions and in amounts effective to prevent or treat Alzheimer's disease or other tauopathies. In certain embodiments, the antibodies are selective for soluble truncated tau protein truncated at (i) its C-terminus after the glutamic acid residue Glu391, or (ii) at the aspartic acid residue Asp421, or (iii) at its N-terminus at the aspartic acid residue Asp13, or (iv) a combination of (i)-(iii). Further aspects of the invention are directed to the administration of an immunogen comprising an abnormal tau, preferably a soluble truncated tau.

1 - 66 . (canceled) 
     
     
         67 . A method of slowing progression of a tangle-related behavioral phenotype in a subject in need of therapy for a tauopathy comprising:
 administering to the subject antibodies selective for an abnormal form of tau,   wherein the abnormal form of tau lacks C-terminus,   the epitope of the antibodies comprises an amino acid sequence of amino acids 2-30 of hTau40, or a portion of the amino acid sequence, and   the antibodies are administered in an amount effective to slow or reverse progression of the tangle-related behavioral phenotype in the subject.   
     
     
         68 . The method of  claim 67 , wherein the epitope of the antibodies consists of the amino acid sequence of amino acids 2-30 of hTau40 or portion of the amino acid sequence. 
     
     
         69 . The method of  claim 67 , wherein the amino acid sequence is selected from SEQ ID NO: 15-23 and portions thereof. 
     
     
         70 . The method of  67 , wherein the antibodies are administered intravenously. 
     
     
         71 . The method of  claim 67 , wherein the tauopathy is Alzheimer's disease. 
     
     
         72 . The method of  67 , wherein the antibodies bind the epitope with equilibrium constant KD of from 1×10 −9  M to 1×10 −11  M, as measured by a surface plasmon resonance assay utilizing peptide captured on strepvidin chip. 
     
     
         73 . A method of slowing progression of a tangle-related behavioral phenotype in a subject in need of therapy for a tauopathy comprising:
 administering to the subject antibodies selective for a synthetic peptide having an amino acid sequence of an N-terminal fragment of hTau40,   wherein the epitope of the antibodies comprises an amino acid sequence of amino acids 2-30 of hTau40, or a portion of the amino acid sequence of amino acids 2-30 of hTau40, and   the antibodies are administered in an amount effective to slow progression of the tangle-related behavioral phenotype in the subject.   
     
     
         74 . The method of  claim 73 , wherein the epitope of the antibodies consists of the amino acid sequence of amino acids 2-30 of hTau40 or portion of the amino acid sequence. 
     
     
         75 . The method of  73 , wherein the antibodies are administered intravenously. 
     
     
         76 . The method of  claim 73 , wherein the tauopathy is Alzheimer's disease. 
     
     
         77 . The method of  claim 73 , wherein the antibodies bind a synthetic peptide of SEQ ID NO: 15, or a portion thereof. 
     
     
         78 . The method of  claim 73 , wherein the antibodies bind the epitope with equilibrium constant KD of from 1×10 −9  M to 1×10 −11  M, as measured by a surface plasmon resonance assay utilizing peptide captured on strepvidin chip. 
     
     
         79 . A method of reducing an amount of a tau fragment in a brain of a subject in need of therapy for a tauopathy comprising:
 administering to the subject antibodies selective for SEQ ID NO: 15, or a portion thereof,   wherein the tau fragment comprises N-terminus of tau, but lack C-terminus of tau, and   the antibodies are administered in an amount effective to reduce the amount of the tau fragment in the subject.   
     
     
         80 . The method of  claim 79 , wherein the epitope of the antibodies consists of SEQ ID NO: 15, or portion thereof. 
     
     
         81 . The method of  79 , wherein the antibodies are administered intravenously. 
     
     
         82 . The method of  claim 79 , wherein the tauopathy is Alzheimer's disease. 
     
     
         83 . The method of  claim 79 , wherein the antibodies are administered before tau is pathologically aggregated. 
     
     
         84 . The method of  claim 79 , wherein the antibodies are administered before pathological NFTs are formed. 
     
     
         85 . The method of  claim 79 , wherein the tau fragment is an N-terminus fragment of hTau40. 
     
     
         86 . The method of  79 , wherein the antibodies bind SEQ ID NO: 15 or portion thereof with equilibrium constant KD of from 1×10 −9  M to 1×10 −11  M, as measured by a surface plasmon resonance assay utilizing peptide captured on strepvidin chip.