Methods for preventing and treating Alzheimer's disease
The present invention relates to methods for preventing and treating Alzheimer's disease (AD). An Aβ42 mimotope is used for vaccination against AD. The mimotope induces the production of antibodies against Aβ42 but not against the native APP. The mimotope is functionally similar to, but not structurally identical with DAEFRH (SEQ ID NO: 1) which is a part of the naturally-occurring Aβ42 sequence.
1. An isolated and purified compound, which 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), and SFEFRG (SEQ ID NO: 115), wherein said compound binds to an antibody specific for DAEFRH (SEQ ID NO: 1) and wherein the compound consists of not more than 15 amino acid residues.
2. The compound of claim 1 , further comprising covalently-coupled carrier.
3. The compound of claim 2 , wherein said carrier is a peptide linker or a polypeptide.
4. The compound of claim 2 , wherein said carrier is selected from the group consisting of KLH, tetanus toxoid, albumin binding protein, bovine serum albumin and dendrimer.
5. A composition comprising the compound of claim 1 and a pharmaceutically acceptable carrier or adjuvant.
6. The composition of claim 5 , which comprises a non-covalently associated peptide linker or protein carrier.
7. The composition of claim 5 , which comprises aluminum hydroxide.
8. The composition of claim 5 which comprises 0.1 ng to 10 mg of said compound.
9. The composition of claim 5 , which comprises 100 ng to 100 μg of said compound.
10. The compound of claim 1 , which comprises EIDYHR (SEQ ID NO: 91).
11. The compound of claim 1 , which comprises ELDYHR (SEQ ID NO: 92).
12. The compound of claim 1 , which comprises EVDYHR (SEQ ID NO: 93).
13. The compound of claim 1 , which comprises DIDYHR (SEQ ID NO: 94).
14. The compound of claim 1 , which comprises DLDYHR (SEQ ID NO: 95).
15. The compound of claim 1 , which comprises DVDYHR (SEQ ID NO: 96).
16. The compound of claim 1 , which comprises DIDYRR (SEQ ID NO: 97).
17. The compound of claim 1 , which comprises DLDYRR (SEQ ID NO: 98).
18. The compound of claim 1 , which comprises DVDYRR (SEQ ID NO: 99).
19. The compound of claim 1 , which comprises DKELRI (SEQ ID NO: 100).
20. The compound of claim 1 , which comprises DWELRI (SEQ ID NO: 101).
21. The compound of claim 1 , which comprises YREFFI (SEQ ID NO: 119).
22. The compound of claim 1 , which comprises YREFRI (SEQ ID NO: 102).
23. The compound of claim 1 , which comprises YAEFRG (SEQ ID NO: 103).
24. The compound of claim 1 , which comprises EAEFRG (SEQ ID NO: 104).
25. The compound of claim 1 , which comprises DYEFRG (SEQ ID NO: 105).
26. The compound of claim 1 , which comprises ELEFRG (SEQ ID NO: 106).
27. The compound of claim 1 , which comprises DRELRI (SEQ ID NO: 107).
28. The compound of claim 1 , which comprises DKELKI (SEQ ID NO: 108).
29. The compound of claim 1 , which comprises DRELKI (SEQ ID NO: 109).
30. The compound of claim 1 , which comprises GREFRN (SEQ ID NO: 110).
31. The compound of claim 1 , which comprises EYEFRG (SEQ ID NO: 111).
32. The compound of claim 1 , which comprises DWEFRDA (SEQ ID NO: 112).
33. The compound of claim 1 , which comprises SWEFRT (SEQ ID NO: 113).
34. The compound of claim 1 , which comprises SFEFRG (SEQ ID NO: 115).