Biomarkers for cognitive dysfunction diseases and method for detecting cognitive dysfunction disease using biomarkers

Abstract

Biomarkers for detecting cognitive dysfunction diseases and methods for detecting cognitive dysfunction diseases using the biomarkers are provided. A method for detecting cognitive dysfunction diseases comprising measuring one or more biomarkers for detecting cognitive dysfunction diseases selected from the following (a), (b), and (c) in a biological sample simultaneously or separately: (a) a biomarker for detecting cognitive dysfunction diseases consisting of an intact protein of apolipoprotein A1 comprising the amino acid sequence represented by SEQ ID NO:1 or a partial peptide thereof; (b) a biomarker for detecting cognitive dysfunction diseases consisting of an intact protein of transthyretin comprising the amino acid sequence represented by SEQ ID NO:2 or a partial peptide thereof; and (c) a biomarker for detecting cognitive dysfunction diseases consisting of an intact protein of complement C3 comprising the amino acid sequence represented by SEQ ID NO:3 or a partial peptide thereof.

1 . A method for detecting cognitive dysfunction diseases comprising
 a measuring step in which amounts of the following three biomarkers (a), (b), and (c) in plasma, serum, or blood of a subject are measured by an anti-Complement C3 antibody, an anti-Apolipoprotein A1 antibody, and an anti-Transthyretin antibody:   (a) a biomarker for detecting cognitive dysfunction diseases consisting of an intact protein of Apolipoprotein A1 comprising the amino acid sequence represented by SEQ ID NO:1 or a partial peptide thereof,   (b) a biomarker for detecting cognitive dysfunction diseases consisting of an intact protein of Transthyretin comprising the amino acid sequence represented by SEQ ID NO:2 or a partial peptide thereof; and   (c) a biomarker for detecting cognitive dysfunction diseases consisting of an intact protein of Complement C3 comprising the amino acid sequence represented by SEQ ID NO:3 or a partial peptide thereof;   a determining step in which whether the subject has mild cognitive impairment is determined on the basis of a combination of the amount of complement C3 and the amount of Transthyretin or Apolipoprotein A1 and whether the subject has Alzheimer's disease is determined on the basis of a combination of the amount of complement C3 and the amount of Transthyretin.   
     
     
         2 . The method for detecting cognitive dysfunction diseases according to  claim 1 ,
 wherein the determining step is conducted using a combination of coefficients including coefficients exhibiting statistical significance and coefficients exhibiting no statistical significance, and   all the coefficients are obtained based on amounts of the three biomarkers obtained by conducting the measuring step on a group of non-demented controls, a group of those having mild cognitive impairment, and a group of those having Alzheimer's disease.   
     
     
         3 . The method for detecting cognitive dysfunction diseases according to  claim 1 ,
 wherein, in the determining step, a reduction of the amount of complement C3 and the amount of Transthyretin or Apolipoprotein A1 is indicative of mild cognitive impairment in the subject and a reduction of the amount of complement C3 and the amount of Transthyretin is indicative of Alzheimer's disease in the subject.   
     
     
         4 . The method for detecting cognitive dysfunction diseases according to  claim 2 , wherein the combination of coefficients is a combination which gives a highest percentage of correct answer. 
     
     
         5 . The method for detecting cognitive dysfunction diseases according to  claim 1 , further comprising
 an applying step in which preventive medicine is applied to the subject, based on a result of the determination in the determining step; or   an evaluating step in which effectiveness of a mental therapy or a medication in the subject is evaluated, based on a result of the determination in the determining step.