Novel biomarkers for cognitive impairment and methods for detecting cognitive impairment using such biomarkers

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 . A method of detecting Complement C4-derived peptide CO4-2 in a patient, said method comprising:
 a. obtaining a biological material from a human patient; and   b. detecting presence or an amount of the Complement C4-derived peptide CO4-2 consisting of amino acid sequence of SEQ ID NO: 22 in the biological material by contacting the biological material with an antibody or aptamer that specifically binds to the peptide CO4-2 and detecting binding between the Complement C4-derived peptide CO4-2 and the antibody or aptamer.   
     
     
         2 . The method of  claim 1 , wherein the biological material is serum, blood, plasma, cerebrospinal fluid, or urine. 
     
     
         3 . A method of diagnosing and treating cognitive impairment in a patient, said method comprising:
 a. obtaining a biological material from a human patient;   b. detecting an amount of Complement C4-derived peptide CO4-2 consisting of amino acid sequence of SEQ ID NO: 22 in the biological material by contacting the biological material with an antibody or aptamer that specifically binds to the peptide CO4-2 and detecting binding between the peptide CO4-2 and the antibody or aptamer;   c. diagnosing the patient with cognitive impairment when a higher amount of the Complement C4-derived peptide CO4-2 in the biological material is detected by comparing the amount of the Complement C4-derived peptide CO4-2 in the patient with an amount of the Complement C4-derived peptide CO4-2 in a biological material obtained from a non-psychiatry disease subject; and   d. administering an effective amount of an anti-acetylcholine esterase inhibitor to the diagnosed patient.   
     
     
         4 . The method of  claim 3 , wherein the biological material is serum, blood, plasma, cerebrospinal fluid, or urine. 
     
     
         5 . The method of  claim 3 , wherein the cognitive impairment includes Alzheimer's dementia, mild cognitive impairment, Dementia with Lewy bodies, and frontotemporal dementia. 
     
     
         6 . The method of  claim 3 , wherein the anti-acetylcholine esterase inhibitor is Donepezil-hydrochloride.