Methods for preventing and treating alzheimer's disease (ad)

Abstract

The present invention relates to methods for preventing Alzheimer's disease (AD) with an Aβ42 mimotope and binds to an antibody specific for DAEFRH (SEQ ID NO: 1) which is a part of the naturally-occurring Aβ42 sequence.

1 - 9 . (canceled) 
     
     
         10 . A method for treating Alzheimer's Disease comprising:
 administering to a subject in need thereof an effective amount of an isolated or purified compound comprising the following amino acid sequence: X 1 X 2 X 3 X 4 X 5 X 6 , wherein
 X 1  is an amino acid other than C (cysteine), 
 X 2  is an amino acid other than C (cysteine), 
 X 3  is an amino acid other than C (cysteine), 
 X 4  is an amino acid other than C (cysteine), 
 X 5  is an amino acid other than C (cysteine), 
 X 6  is an amino acid other than C (cysteine), wherein said compound binds to an antibody specific for DAEFRH (SEQ ID NO: 1), but wherein X 1 X 2 X 3 X 4 X 6  is not DAEFRH (SEQ ID NO: 1). 
   
     
     
         11 . The method of  claim 10 , wherein
 X 1  is an amino acid with a hydroxy group or a negatively charged amino acid,   X 2  is a hydrophobic amino acid or a positively charged amino acid,   X 3  is a negatively charged amino acid,   X 4  is an aromatic amino acid,   X 5  is H, K, Y, F or R, and   X 6  is S, T, N, Q, D, E, R, I, K, Y, or G.   
     
     
         12 . The method of  claim 10 , wherein
 X 1  is G, E, Y, S or D,   X 2  is I, L, V, K, W, R, Y, F or A,   X 3  is D or E,   X 4  is Y, F or L,   X 5  is H, F or R, and   X 6  is T, N, D, R, I or G.   
     
     
         13 . The method of  claim 10 , wherein the compound comprises a sequence selected from the group consisting of EIDYHR (SEQ ID NO: 91), ELDYHR (SEQ ID NO: 92), EVDYHR (SEQ ID NO: 93), DIDYHR (SEQ ID NO: 94), DLDYHR (SEQ ID NO: 95), DVDYHR (SEQ ID NO: 96), DIDYRR (SEQ ID NO: 97), DLDYRR (SEQ ID NO: 98), DVDYRR (SEQ ID NO: 99), DKELRI (SEQ ID NO: 100), DWELRI (SEQ ID NO: 101), YREFFI (SEQ ID NO: 119), YREFRI (SEQ ID NO: 102), YAEFRG (SEQ ID NO: 103), EAEFRG (SEQ ID NO: 104), DYEFRG (SEQ ID NO: 105), ELEFRG (SEQ ID NO: 106), DRELRI (SEQ ID NO: 107), DKELKI (SEQ ID NO: 108), DRELKI (SEQ ID NO: 109), GREFRN (SEQ ID NO: 110), EYEFRG (SEQ ID NO: 111), DWEFRDA (SEQ ID NO: 112), SWEFRT (SEQ ID NO: 113), DKELR (SEQ ID NO: 114) and SFEFRG (SEQ ID NO: 115). 
     
     
         14 . The method of  claim 13 , wherein the compound comprises DWELRI (SEQ ID NO: 101). 
     
     
         15 . The method of  claim 13 , wherein the compound comprises DYEFRG (SEQ ID NO: 105). 
     
     
         16 . The method of  claim 13 , wherein the compound comprises ELEFRG (SEQ ID NO: 106). 
     
     
         17 . The method of  claim 13 , wherein the compound comprises DKELKI (SEQ ID NO: 108). 
     
     
         18 . The method of  claim 13 , wherein the compound comprises SWEFRT (SEQ ID NO: 113). 
     
     
         19 . The method of  claim 13 , wherein the compound comprises DKELR (SEQ ID NO: 114). 
     
     
         20 . The method of  claim 13 , wherein the compound comprises SFEFRG (SEQ ID NO: 115). 
     
     
         21 . The method of  claim 10 , wherein the compound consists of 5 to 15 amino acid residues. 
     
     
         22 . The method of  claim 10 , wherein the compound is covalently-coupled to a carrier. 
     
     
         23 . The method of  claim 22 , wherein said carrier is a peptide linker or a polypeptide. 
     
     
         24 . The method of  claim 22 , wherein said carrier is selected from the group consisting of KLH, tetanus toxoid, albumin binding protein, bovine serum albumin and dendrimer. 
     
     
         25 . A method for isolating a compound binding to an antibody specific for the natural N-terminal A942 sequence DAEFRH (SEQ ID NO: 1) comprising: providing a peptide compound library comprising peptides containing the following amino acid sequence
 X 1 X 2 X 3 X 4 X 5 X 6 , wherein   X 1  is an amino acid other than C (cysteine),   X 2  is an amino acid other than C (cysteine),   X 3  is an amino acid other than C (cysteine),   X 4  is an amino acid other than C (cysteine),   X 5  is an amino acid other than C (cysteine),   X 6  is an amino acid other than C (cysteine),   wherein X 1 X 2 X 3 X 4 X 6  is not DAEFRH (SEQ ID NO: 1); contacting said peptide library with an antibody which binds to DAEFRH (SEQ ID NO: 1); and isolating those members of the peptide library which bind to said antibody.   
     
     
         26 . The method of  claim 25 , wherein said peptides are provided in individualized form in said library or are immobilized separately on a solid surface. 
     
     
         27 . The method of  claim 25 , wherein said antibody comprises a marker which allows its detection or isolation when bound to a peptide in the library.