Treatment agent for cognitive impairment induced by amyloid beta-protein, therapeutic agent for alzheimer's disease, and treatment method and pathological analysis method related to these

Abstract

The present invention aims to provide an anti-Alzheimer's disease agent based on an action mechanism associated with amyloid β protein, which action mechanism is different from conventional action mechanisms. The therapeutic drug for Alzheimer's disease according to the present invention contains a therapeutic agent for cognitive impairment induced by amyloid β protein, which therapeutic agent comprises a peptide having the amino acid sequence represented by SEQ ID NO:1 or a peptide similar to this peptide, especially a peptide containing the amino acid sequence represented by SEQ ID NO:2, which is a partial sequence of SEQ ID NO:1. (SEQ ID NO: 1) VLSSQQFLHRGHQPPPEMAGHSLASSHRNSMIPSAAT (SEQ ID NO: 2) HRGHQPPPEMA

1 . A therapeutic agent for cognitive impairment induced by amyloid β protein, comprising as an effective component a peptide corresponding to any one of the following (I) to (VI):
 (I) a peptide consisting of the amino acid sequence represented by SEQ ID NO:1: 
 
       
         
           
                 
                 
               
                     
                   (SEQ ID NO: 1) 
                 
                     
                   VLSSQQFLHRGHQPPPEMAGHSLASSHRNSMIPSAAT; 
                 
             
                
                
               
            
           
         
         (II) a peptide consisting of the same amino acid sequence as the amino acid sequence represented by SEQ ID NO:1 except that one to three amino acids are altered by any one or more of deletion, addition, substitution, and side-chain modification; 
         (III) a peptide consisting of a partial sequence of the amino acid sequence represented by SEQ ID NO:1, comprising the amino acid sequence represented by SEQ ID NO:2: 
       
       
         
           
                 
                 
                 
               
                     
                   HRGHQPPPEMA; 
                   (SEQ ID NO: 2) 
                 
             
                
               
            
           
         
         (IV) a peptide consisting of the same amino acid sequence as a partial sequence of the amino acid sequence represented by SEQ ID NO:1 comprising the amino acid sequence represented by SEQ ID NO:2, except that one or two amino acids are altered by any one or more of deletion, addition, substitution, and side-chain modification; 
         (V) a peptide consisting of an amino acid sequence comprising the amino acid sequence represented by SEQ ID NO:2, wherein a total of 1 to 50 amino acids are added to the N-terminus and/or the C-terminus of the amino acid sequence represented by SEQ ID NO:2 (excluding amino acid sequences which are identical to all or part of the amino acid sequence represented by SEQ ID NO:1); and 
         (VI) a peptide consisting of an amino acid sequence comprising the same amino acid sequence as the amino acid sequence represented by SEQ ID NO:2 except that one or two amino acids are altered by any one or more of deletion, addition (excluding addition to the N-terminus and/or the C-terminus), substitution, and side-chain modification, wherein a total of 1 to 50 amino acids are added to the N-terminus and/or the C-terminus of said altered amino acid sequence. 
       
     
     
         2 . A therapeutic drug for Alzheimer's disease, comprising the therapeutic agent according to  claim 1 . 
     
     
         3 . A method for treatment of cognitive impairment induced by amyloid β protein, comprising a step of administering the therapeutic agent according to  claim 1  to a mammal (excluding human) which developed cognitive impairment induced by amyloid β protein or to a model animal thereof. 
     
     
         4 . A method for treatment of Alzheimer's disease, comprising a step of administering the therapeutic drug according to  claim 2  to a mammal (excluding human) which developed Alzheimer's disease or to a model animal thereof. 
     
     
         5 . A method for pathological analysis of cognitive impairment induced by amyloid β protein, comprising a step of administering a peptide corresponding to any one of the above (I) to (VI) to a mammal (excluding human) which developed cognitive impairment induced by amyloid β protein or to a model animal thereof, or a step of adding said peptide to a cultured nerve cell(s) as a model cell(s) thereof or to a biomolecule(s) expressed in a nerve cell(s). 
     
     
         6 . A method for pathological analysis of Alzheimer's disease, comprising a step of administering a peptide corresponding to any one of the above (I) to (VI) to a mammal (excluding human) which developed Alzheimer's disease or to a model animal thereof, or a step of adding said peptide to a cultured nerve cell(s) as a model cell(s) thereof or to a biomolecule(s) expressed in a nerve cell(s).