Soluble low-density lipoprotein receptor related protein binds directly to alzheimer's amyloid-beta peptide

Abstract

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 - 17 . (canceled) 
     
     
         18 . A method of binding amyloid-β peptide (Aβ) in a body fluid and/or tissue of a subject, said method comprising:
 (a) administering 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 and   (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 by said soluble LRP-1 derivative.   
     
     
         19 . The method of  claim 18 , wherein said soluble LRP-1 derivative binds said Aβ inside said subject's body. 
     
     
         20 . The method of  claim 18 , wherein said soluble LRP-1 derivative binds said Aβ outside said subject's body. 
     
     
         21 . (canceled) 
     
     
         22 . The method of  claim 18 , wherein soluble LRP-1 derivative bound to AP is inactivated such that amyloid deposits are reduced in said subject's body. 
     
     
         23 - 28 . (canceled) 
     
     
         29 . The method of  claim 18 , wherein said soluble LRP-1 derivative is comprised of cluster II. 
     
     
         30 . The method of  claim 18 , wherein said soluble LRP-1 derivative is comprised of cluster IV. 
     
     
         31 . The method of  claim 18 , wherein said soluble LRP-1 derivative consists essentially of cluster II, cluster IV, or both. 
     
     
         32 . The method of  claim 18 , wherein said soluble LRP-1 derivative is comprised of at least one domain which mediates secretion. 
     
     
         33 . The method of  claim 18 , wherein said soluble LRP-1 derivative is not comprised of a domain which mediates attachment to a lipid bilayer. 
     
     
         34 . The method of  claim 18 , wherein said soluble LRP-1 derivative is reversibly attached to a solid substrate. 
     
     
         35 . The method of  claim 18 , wherein said soluble LRP-1 derivative is irreversibly attached to a solid substrate. 
     
     
         36 . The method of  claim 18 , wherein said soluble LRP-1 derivative is derived from human. 
     
     
         37 . The method of  claim 18 , wherein said soluble LRP-1 derivative does not elicit an immune response in human. 
     
     
         38 . The method of  claim 18 , wherein said soluble LRP-1 derivative further comprises at least one heterologous domain. 
     
     
         39 . The method of  claim 18 , wherein at least one detectable label is covalently attached to said soluble LRP-1 derivative. 
     
     
         40 . The method of  claim 38 , wherein at least one detectable label is covalently attached to a heterologous domain of said soluble LRP-1 derivative. 
     
     
         41 . The method of  claim 18 , wherein said soluble LRP-1 derivative is comprised of both cluster II and cluster IV. 
     
     
         42 . A method of binding amyloid-β peptide (Aβ) in a body fluid of a human subject, said method comprising:
 (a) administering a soluble fragment of human low-density lipoprotein receptor related protein-1 (LRP-1) comprising cluster II, cluster IV, or both and (b) contacting said soluble LRP-1 fragment with at least said body fluid of said human subject such that said Aβ is specifically bound by said soluble fragment of human LRP-1.   
     
     
         43 . The method of  claim 42 , wherein soluble LRP-1 derivative bound to Aβ is inactivated such that amyloid deposits are reduced in said human subject's body. 
     
     
         44 . A method of binding amyloid-β peptide (Aβ) in a human subject, said method comprising administering an effective amount of a soluble fragment of human low-density lipoprotein receptor related protein-1 (LRP-1) comprising cluster II, cluster IV, or both such that said Aβ is specifically bound by said soluble fragment of human LRP-1.