Chromosome 1 gene and gene products related to alzheimer's disease

Abstract

The present invention discloses nucleic acid molecules encoding AD4 gene products, expression vectors and host cells suitable for expressing such gene products. Also disclosed are methods for treating, preventing, and diagnosing Alzheimer's Disease.

We claim:  
     
         1 . An isolated nucleic acid molecule encoding an AD4 gene product.  
     
     
         2 . The isolated nucleic acid molecule of  claim 1  wherein said molecule is set forth in FIG. 1.  
     
     
         3 . The isolated nucleic acid molecule of  claim 1  wherein said nucleic acid molecule encodes a mutant AD4 gene product that increases the probability of Alzheimer's Disease.  
     
     
         4 . The isolated nucleic acid molecule of  claim 3  wherein said nucleic acid molecule encodes a mutant AD4 gene product with an amino acid subsitution at residue 141.  
     
     
         5 . The isolated nucleic acid molecule of  claim 4  wherein said substitution at residue 141 is an aspargine to isoleucine substitution.  
     
     
         6 . An isolated nicleic acid molecule selected from the group consisting of: 
 (a) an isolated nucleic acid molecule as set forth in FIG. 1 or complementary sequence thereof;    (b) an isolated nucleic acid molecule that specifically hybridizes to the nucleic acid molecule of (a) under conditions of high stringency; and    (c) an isolated nucleic acid that encodes an AD4 gene product.    
     
     
         7 . An expression vector, comprising a promoter operably linked to a nucleic acid molecule according to any one of  claims 1  to  6 .  
     
     
         8 . The expression vector according to  claim 7  wherein said promoter is selected from the group consisting of CMV I-E promoter, SV40 early promoter and MuLV LTR.  
     
     
         9 . The expression vector according to  claim 7  wherein said promoter is a tissue-specific promoter.  
     
     
         10 . A viral vector capable of directing the expression of a nucleic acid molecule according to any one of  claims 1  to  6 .  
     
     
         11 . The viral vector according to  claim 10  wherein said vector is selected from the group consisting of herpes simplex viral vectors, adenoviral vectors, adenovirus-associated viral vectors and retroviral vectors.  
     
     
         12 . A host cell carrying a vector according to any one of  claims 7  to  11 .  
     
     
         13 . The host cell according to  claim 12  wherein said cell is selected from the group consisting of human cell, dog cell, monkey cell, rat cell and mouse cell.  
     
     
         14 . An isolated protein comprising an AD4 gene product.  
     
     
         15 . The isolated protein of  claim 14  wherein said protein consists essentially of an AD4 gene product.  
     
     
         16 . The isolated protein of  claim 14  wherein said protein has an amino acid sequence set forth in FIG. 2.  
     
     
         17 . The isolated protein of  claim 14  wherein said protein is a mutant AD4 gene product that increases the probability of Alzheimer's Disease.  
     
     
         18 . The isolated protein of  claim 17  wherein said mutant AD4 gene product has an amino acid subsitution at residue 141.  
     
     
         19 . The isolated protein of  claim 17  wherein said substitution at residue 141 is an aspargine to isoleucine substitution.  
     
     
         20 . A method of treating or preventing Alzheimer's Disease, comprising administering to a patient a vector containing or expressing a nucleic acid molecule according to any one of claims  1 ,  2 , or  6 , thereby reducing the likelihood or delaying the onset of Alzheimer's Disease in said patient.  
     
     
         21 . A method of treating or preventing Alzheimer's Disease, comprising administering to a patient a protein according to any one of  claims 14  to  23 , thereby reducing the likelihood or delaying the onset of Alzheimer's Disease in said patient.  
     
     
         22 . A method of treating or preventing Alzheimer's Disease, comprising administering to a patient an antibody specific for a protein according to any one of  claims 17  to  19 , thereby reducing the likelihood or delaying the onset of Alzheimer's Disease in said patient.  
     
     
         23 . The method according to any one of claims  20 - 22  wherein said method comprises in vivo administration.  
     
     
         24 . A pharmaceutical composition comprising a vector comprising the nucleic acid molecule according to any one of claims  1  and  2 , along with a pharmaceutically acceptable carrier or diluent.  
     
     
         25 . A pharmaceutical composition comprising a host cell according to any one of claims  12  and  13 , along with a pharmaceutically acceptable carrier or diluent.  
     
     
         26 . A pharmaceutical composition comprising a protein according to any one of  claims 14  to  16 , along with a pharmaceutically acceptable carrier or diluent.  
     
     
         27 . An antibody which specifically binds to the protein according to any one of  claims 14  to  19 .  
     
     
         28 . The antibody according to  claim 27  wherein the antibody is a monoclonal antibody.  
     
     
         29 . The antibody according to  claim 28  wherein the antibody is selected from the group consisting of an Fab fragment, an Fv fragment and a single chain antibody.  
     
     
         30 . A hybridoma capable of producing the antibody according to  claim 28 .  
     
     
         31 . A pharmaceutical composition comprising an antibody according to  claim 27 , along with a pharmaceutically acceptable carrier or diluent.  
     
     
         32 . A nucleic acid probe which is capable of specifically hybridizing to an AD4 gene under conditions of high stringency.  
     
     
         33 . A nucleic acid probe comprising at least a portion of the nucleotide sequence shown in FIG. 1 or its complementary sequence, said probe being capable of specifically hybridizing to a mutant AD4 gene under conditions of high stringency.  
     
     
         34 . A probe comprising at least a portion of the nucleotide sequence shown in FIG. 1 or its complementary sequence, said probe being capable of specifically hybridizing to a mutant AD4 gene, in which amino acid residue 141 is changed from asparagine to isoleucine, under conditions of very high stringency.  
     
     
         35 . The probe according to any one of  claims 32  to  34  wherein said probe comprises at least 12 nucleotide bases  
     
     
         36 . A pair of primers capable of specifically amplifying all or a portion of a nucleic acid molecule according to any one  claims 1  to  6 .  
     
     
         37 . The primer according to  claim 36  wherein said primer comprises at least 12 nucleotide bases.  
     
     
         38 . A method of diagnosing a patient having an increased likelihood of contracting Alzheimer's Disease, comprising: 
 (a) obtaining from a patient a biological sample containing nucleic acid;    (b) incubating the nucleic acid with a probe which is capable of specifically hybridizing to a mutant AD4 gene under conditions and for time sufficient to allow hybridization to occur; and    (c) detecting the presence of hybridized probe, and thereby determining that said patient has an increased likelihood of contracting Alzheimer's Disease.    
     
     
         39 . A method of diagnosing a patient having an increased likelihood of contracting Alzheimer's Disease, comprising: 
 (a) obtaining from a patient a biological sample containing nucleic acid;    (b) amplifying a selected nucleic acid sequence associated with a mutant AD4 gene; and    (c) detecting the presence of an amplified nucleic acid sequence, and thereby determining that said patient has an increased likelihood of contracting Alzheimer's Disease.    
     
     
         40 . A method of diagnosing a patient having an increased likelihood of contracting Alzheimer's Disease, comprising: 
 (a) contacting a biological sample obtained from a patient with an antibody that specifically binds to a mutant AD4 protein, under conditions and for a time sufficient to allow binding of the antibody to the protein; and    (b) detecting the presence of the bound antibody.    
     
     
         41 . A peptide vaccine comprising a portion of a mutant AD4 gene product containing a mutation, in combination with a pharmaceutically acceptable carrier or diluent.  
     
     
         42 . A transgenic animal whose germ cells and somatic cells contain an AD4 gene which is operably linked to a promoter effective for the expression of said gene, said gene being introduced into said animal, or an ancestor of said animal, at an embryonic stage.  
     
     
         43 . The transgenic animal according to  claim 42  wherein the animal is selected from the group consisting of a mouse, a rat and a dog.  
     
     
         44 . The transgenic animal according to  claim 42  wherein AD4 is expressed from a vector according to any one of  claims 7  to  11   
     
     
         45 . The transgenic animal according to  claim 42  wherein the AD4 gene encodes a mutant AD4 gene product.  
     
     
         46 . An isolated DNA molecule comprising AD4 gene sequence presented in FIGS.  13  to  19 .