Test and model for Alzheimer's disease

Abstract

The invention provides an isolated nucleic acid characteristic of human amyloid precursor protein 770 including the nucleotides encoding codon 670 and 671, wherein the nucleic acid encodes an amino acid other than lysine at codon 670 and/or an amino acid other than methionine at codon 671. Also provided is a method of diagnosing or predicting a predisposition to Alzheimer's disease, comprising detecting in a sample from a subject the presence of a mutation at a nucleotide position corresponding to codons 670 and/or 671 of amyloid precursor protein or fragment thereof, the presence of the mutation indicating the presence of or a predisposition to Alzheimer's disease.

1 - 20 . (canceled)  
     
     
         21 . A transgenic non-human animal comprising, in a germ or somatic cell, a nucleic acid encoding human amyloid precursor protein including the nucleotides encoding codon 670 and 671 of human amyloid precursor protein 770, or encoding the codons corresponding to these in other isoforms of APP, operably linked to a promoter, wherein the nucleic acid encodes an amino acid other than lysine at codon 670 and/or an amino acid other than methionine at codon 671 and, wherein the animal expresses a human amyloid precursor protein or fragment thereof which has an amino acid other than lysine at codon 670 and/or an amino acid other than methionine at codon 671.  
     
     
         22 . The animal of  claim 21 , wherein the animal is useful for the study of the biochemistry of amyloid precursor protein (APP) and β-amyloid metabolism.  
     
     
         23 . A transgenic non-human animal comprising, in a germ or somatic cell, a nucleic acid encoding human amyloid precursor protein including the nucleotides encoding codon 670, 671 and 717 of human amyloid precursor protein 770, or encoding the codons corresponding to these in other isoforms of APP, operably linked to a promoter, wherein the nucleic acid encodes an amino acid other than lysine at codon 670 and/or an amino acid other than methionine at codon 671 and an amino acid other than valine at codon 717 and, wherein the animal expresses a human amyloid precursor protein or fragment thereof which has an amino acid other than lysine at codon 670 and/or an amino acid other than methionine at codon 671 and an amino acid other than valine at codon 717.  
     
     
         24 . The animal of  claim 23 , wherein the animal is useful for the study of the biochemistry of amyloid precursor protein (APP) and β-amyloid metabolism.  
     
     
         25 - 28 . (canceled)  
     
     
         29 . A method of screening for an agent for treating Alzheimer's disease comprising contacting the animal of  claim 22  with the agent and monitoring the expression, processing or deposition of amyloid precursor protein or fragments thereof.  
     
     
         30 . A method of screening for an agent for treating Alzheimer's disease comprising contacting the animal of  claim 24  with the agent and monitoring the expression, processing or deposition of amyloid precursor protein or fragments thereof.  
     
     
         31 - 32 . (canceled)