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 . A biomarker for detection of cognitive impairment comprising at least one protein or peptide selected from the group consisting of Complement C3 consisting of amino acid sequence expressed by SEQ ID NO: 1, Transcription factor AP-2 gamma consisting of amino acid sequence expressed by SEQ ID NO: 3, Synapsin-3 consisting of amino acid sequence expressed by SEQ ID NO: 5, Oxytocin receptor consisting of amino acid sequence expressed by SEQ ID NO: 7, Inter-alpha-trypsin inhibitor heavy chain H5-like protein consisting of amino acid sequence expressed by SEQ ID NO: 9, E3 ubiquitin-protein ligase HERC2 consisting of amino acid sequence expressed by SEQ ID NO: 11, Prothrombin consisting of amino acid sequence expressed by SEQ ID NO: 13, Transthyretin consisting of amino acid sequence expressed by SEQ ID NO: 15, Tumor necrosis factor receptor superfamily member 16 consisting of amino acid sequence expressed by SEQ ID NO: 17, Complement C4-A consisting of amino acid sequence expressed by SEQ ID NO: 19, Complement C4-B consisting of amino acid sequence expressed by SEQ ID NO: 21, Fibrinogen alpha chain (isoform 1) consisting of amino acid sequence expressed by SEQ ID NO: 23, and Fibrinogen alpha chain (isoform 2) consisting of amino acid sequence expressed by SEQ ID NO: 25. 
     
     
         2 . A biomarker for detection of cognitive impairment comprising the peptide selected from the group consisting of Complement C3-derived peptide CO3 consisting of amino acid sequence expressed by SEQ ID NO: 2, Transcription factor AP-2 gamma-derived peptide AP2C consisting of amino acid sequence expressed by SEQ ID NO: 4, Synapsin-3-derived peptide SYN3 consisting of amino acid sequence expressed by SEQ ID NO: 6, Oxytocin receptor-derived peptide OXYR consisting of amino acid sequence expressed by SEQ ID NO: 8, Inter-alpha-trypsin inhibitor heavy chain H5-like protein-derived peptide ITH5L consisting of amino acid sequence expressed by SEQ ID NO: 10, E3 ubiquitin-protein ligase HERC2-derived peptide HERC2 consisting of amino acid sequence expressed by SEQ ID NO: 12, Prothrombin-derived peptide THRB consisting of amino acid sequence expressed by SEQ ID NO: 14, Transthyretin-derived peptide TTHY consisting of amino acid sequence expressed by SEQ ID NO: 16, Tumor necrosis factor receptor superfamily member 16-derived peptide TNR16 consisting of amino acid sequence expressed by SEQ ID NO: 18, Complement C4-derived peptide CO4-1 consisting of amino acid sequence expressed by SEQ ID NO: 20, Complement C4-derived peptide CO4-2 consisting of amino acid sequence expressed by SEQ ID NO: 22, Fibrinogen alpha chain-derived peptide FIBA-1 consisting of amino acid sequence expressed by SEQ ID NO: 24, Fibrinogen alpha chain-derived peptide FIBA-2 consisting of amino acid sequence expressed by SEQ ID NO: 26, and Fibrinogen alpha chain-derived peptide FIBA-3 consisting of amino acid sequence expressed by SEQ ID NO: 27. 
     
     
         3 . A biomarker of cognitive impairment comprising the peptides selected from the group 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 that is appeared or increased in biological material of patients of cognitive impairment as compared to biological material of subjects not suffering from psychiatry disease. 
     
     
         4 . A biomarker of Alzheimer disease comprising the peptides selected from the group 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 that is appeared or increased in biological material of patients of Alzheimer disease as compared to biological material of subjects not suffering from psychiatry disease. 
     
     
         5 . A biomarker of mild cognitive impairment comprising the peptides selected from the group 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 that is appeared or increased in biological material of patients of mild cognitive impairment as compared to biological material of subjects not suffering from psychiatry disease. 
     
     
         6 . Method for detection of cognitive impairment involving determination in biological material of at least one biomarker for cognitive impairment described in  claim 1 . 
     
     
         7 . Method for detection of psychiatry disease described in  claim 6  wherein detection is made either by immunoblot procedure, Western blotting, enzyme-, fluorescence-, or radioisotope-labeled antibody method, mass spectrometry, immunoMS method or surface plasmon resonance method. 
     
     
         8 . A kit for detection of cognitive impairment to determine at least one biomarker described in  claim 1 . 
     
     
         9 . A kit for detection of psychiatry disease containing antibody or aptamer to at least one biomarker described in  claim 1 .