Biomarker for cognitive dysfunction diseases, and method for detection of cognitive dysfunction diseases using the biomarker

Abstract

The present invention aims to provide methods to detect cognitive impairment including mild cognitive impairment and Alzheimer disease by using a protein or its partial peptide that differs in presence or absence, or in quantity between non-cognitive impairment and patients with cognitive impairment and further aims to present biomarkers comprising said protein and said partial peptide to be used to detect cognitive impairment including Alzheimer disease or mild cognitive impairment. Specifically, a biomarker for diagnosis of psychiatry disease or cognitive impairment comprising protein fragment or peptide of not less than 5 amino acid residues arising from at least one protein or peptide selected from the group of proteins consisting of amino acid sequence expressed by SEQ ID NOS: 1, 3, 5, 7, 9, 11, 13, 15, 17, 19, 21, 23, and 25 and selected from the group of partial peptide in these proteins consisting of amino acid sequence expressed by SEQ ID NOS: 2, 4, 6, 8, 10, 12, 14, 16, 18, 20, 22, 24, 26, and 27. And further aims to provide diagnostic method using these biomarker.

1 . An antibody that specifically binds to a Prothrombin-derived peptide comprising SEQ ID NO: 14. 
     
     
         2 . The antibody according to  claim 1 , wherein said antibody further comprises a detectable label. 
     
     
         3 . The antibody according to  claim 2 , wherein said label is selected from the group consisting of an enzyme, a chemiluminescent substance, a fluorescent substance and a radioisotope. 
     
     
         4 . A solid support having an antibody that specifically binds to a peptide of SEQ ID NO: 14. 
     
     
         5 . The solid support according to  claim 4 , wherein said solid support is a plate. 
     
     
         6 . The solid support according to  claim 4 , wherein said solid support is a bead. 
     
     
         7 . The solid support of  claim 6 , wherein said bead is a magnetic bead. 
     
     
         8 . A kit for testing whether a subject has cognitive impairment, comprising:
 an antibody that specifically binds to a polypeptide comprising the amino acid sequence of SEQ ID NO: 14; and   at least one additional component selected from the group consisting of a buffer to dilute a biological sample from said subject to be tested and a secondary antibody that binds to said antibody.   
     
     
         9 . The kit of  claim 8 , which comprises said secondary antibody that binds to the antibody. 
     
     
         10 . The kit of  claim 9 , wherein said secondary antibody is conjugated to a label. 
     
     
         11 . The kit of  claim 10 , wherein said label is selected from the group consisting of an enzyme, a chemiluminescent substance, a fluorescent substance and a radioisotope. 
     
     
         12 . The kit of  claim 9 , further comprising a solid support that has the antibody immobilized thereon. 
     
     
         13 . The kit of  claim 12 , wherein the solid support is a plate. 
     
     
         14 . The kit of  claim 12 , wherein the solid support is a bead. 
     
     
         15 . The kit of  claim 14 , wherein the bead is a magnetic bead. 
     
     
         16 . A method for detection of cognitive impairment comprising:
 contacting a biological sample from a subject to be tested for cognitive impairment with an antibody that specifically binds to the peptide of SEQ ID NO: 14; and   determining if said antibody specifically binds to a said peptide in said sample, wherein specific binding of the antibody to said component in said sample indicates that the subject has cognitive impairment.   
     
     
         17 . The method for detection according to  claim 16 , wherein the antibody is attached to a bead or plate. 
     
     
         18 . The method for detection according to  claim 16 , wherein specific binding to a component in said sample indicates that the subject has Alzheimer's disease. 
     
     
         19 . The method for detection according to  claim 16 , wherein said determining is made by an immunoblot procedure, Western blotting, enzyme-labeled antibody method, fluorescence-labeled antibody method, radioisotope-labeled antibody method, mass spectrometry, immunoMS method or surface plasmon resonance method.