Soluble low-density lipoprotein receptor related protein binds directly to Alzheimer's amyloid-beta peptide
View Patent ↗A soluble derivative of low-density lipoprotein receptor related protein-1 (sLRP-1) binds directly to Alzheimer's amyloid-β peptide (Aβ). This binding may be used to detect Aβ or to separate Aβ from the rest of a subject's body. In Alzheimer's disease, it may be used to provide diagnostic results by detecting Aβ, treatment by removing Aβ, or both.
1. A method of binding amyloid-β peptide (Aβ) in a body fluid and/or tissue of a subject, said method comprising:
(a) providing a soluble derivative of low-density lipoprotein receptor related protein-1 (LRP-1), wherein said soluble LRP-1 derivative is comprised of cluster II, cluster IV, or both;
(b) contacting said soluble LRP-1 derivative with at least said body fluid and/or tissue of said subject such that said Aβ is specifically bound; and
(c) detecting said soluble LRP-1 derivative bound to Aβ.
2. The method of claim 1 , wherein said soluble LRP-1 derivative binds said Aβ inside said subject's body.
3. The method of claim 1 , wherein said soluble LRP-1 derivative binds said Aβ outside said subject's body.
4. The method of claim 1 , wherein said soluble LRP-1 derivative bound to Aβ is removed from said subject's body.
5. The method of claim 1 , wherein said soluble LRP-1 derivative bound to Aβ is inactivated such that amyloid deposits are reduced in said subject's body.
6. The method of claim 1 , wherein said soluble LRP-1 derivative is comprised of cluster II.
7. The method of claim 1 , wherein said soluble LRP-1 derivative is comprised of cluster IV.
8. The method of claim 1 , wherein said soluble LRP-1 derivative consists essentially of cluster II, cluster IV, or both.
9. The method of claim 1 , wherein said soluble LRP-1 derivative is comprised of at least one domain which mediates secretion.
10. The method of claim 1 , wherein said soluble LRP-1 derivative is not comprised of a domain which mediates attachment to a lipid bilayer.
11. The method of claim 1 , wherein said soluble LRP-1 derivative is reversibly attached to a solid substrate.
12. The method of claim 1 , wherein said soluble LRP-1 derivative is irreversibly attached to a solid substrate.
13. The method of claim 1 , wherein said soluble LRP-1 derivative is derived from human.
14. The method of claim 1 , wherein said soluble LRP-1 derivative does not elicit an immune response in a human.
15. The method of claim 1 , wherein said soluble LRP-1 derivative further comprises at least one heterologous domain.
16. The method of claim 15 , wherein at least one detectable label is covalently attached to heterologous domain.
17. The method of claim 1 , wherein at least one detectable label is covalently attached to said soluble LRP-1 derivative.
18. The method of claim 1 , wherein said soluble LRP-1 derivative is comprised of both cluster II and cluster IV.
19. A method of binding amyioid-β peptide (Aβ) in a body fluid of a human subject, said method comprising:
(a) providing a soluble fragment of low-density lipoprotein receptor related protein-1 (LRP-1) comprising cluster II, cluster IV, or both of human LRP-1;
(b) contacting said soluble fragment of LRP-1 with at least said body fluid of said human subject such that said Aβ is specifically bound; and
(c) detecting said soluble fragment of LRP-1 bound to Aβ.
20. The method of claim 19 , wherein said soluble fragment of LRP-1 bound to Aβ is removed from said human subject's body.
21. The method of claim 19 , wherein said soluble fragment of LRP-1 bound to Aβ is inactivated such that amyloid deposits are reduced in said human subject's body.
22. A method of binding amyloid-β peptide (Aβ) in a body fluid and/or tissue of a subject, said method comprising:
(a) providing a soluble derivative of low-density lipoprotein receptor related protein-1 (LRP-1), wherein said soluble LRP-1 derivative is comprised of cluster II, cluster IV, or both;
(b) contacting said soluble LRP-1 derivative with at least said body fluid and/or tissue of said subject such that said Aβ is specifically bound; and
(c) removing said soluble LRP-1 derivative bound to Aβ from said subject's body.
23. The method of claim 22 , wherein said soluble LRP-1 derivative binds said Aβ inside said subject's body.
24. The method of claim 22 , wherein said soluble LRP-1 derivative binds said Aβ outside said subject's body.
25. The method of claim 22 , wherein said soluble LRP-1 derivative bound to Aβ is inactivated such that amyloid deposits are reduced in said subject's body.
26. The method of claim 22 , wherein said soluble LRP-1 derivative is comprised of cluster lI.
27. The method of claim 22 , wherein said soluble LRP-1 derivative is comprised of cluster IV.
28. The method of claim 22 , wherein said soluble LRP-1 derivative consists essentially of cluster II, cluster IV, or both.
29. The method of claim 22 , wherein said soluble LRP-1 derivative is comprised of at least one domain which mediates secretion.
30. The method of claim 22 , wherein said soluble LRP-1 derivative is not comprised of a domain which mediates attachment to a lipid bilayer.
31. The method of claim 22 , wherein said soluble LRP-1 derivative is reversibly attached to a solid substrate.
32. The method of claim 22 , wherein said soluble LRP-1 derivative is irreversibly attached to a solid substrate.
33. The method of claim 22 , wherein said soluble LRP-1 derivative is derived from human.
34. The method of claim 22 , wherein said soluble LRP-1 derivative does not elicit an immune response in a human.
35. The method of claim 22 , wherein said soluble LRP-1 derivative further comprises at least one heterologous domain.
36. The method of claim 35 , wherein at least one detectable label is covalently attached to said heterologous domain.
37. The method of claim 22 , wherein at least one detectable label is covalently attached to said soluble LRP-1 derivative.
38. The method of claim 22 , wherein said soluble LRP-1 derivative is comprised of both cluster II and cluster IV.
39. A method of binding amyloid-β peptide (Aβ) in a body fluid of a human subject, said method comprising:
(a) providing a soluble fragment of low-density lipoprotein receptor related protein-1 (LRP-1) comprising cluster II, cluster IV, or both of human LRP-1;
(b) contacting said soluble fragment of LRP-1 with at least said body fluid of said human subject such that said Aβ is specifically bound; and
(c) removing said soluble fragment of LRP-1 derivative bound to Aβ from said subject's body.
40. The method of claim 39 , wherein said soluble fragment of LRP-1 derivative bound to Aβ is inactivated such that amyloid deposits are reduced in said human subject's body.