Biomarkers for diagnosing alzheimer's disease

Abstract

A method for assessing the state of Alzheimer's disease in patients is disclosed. A method for monitoring the progression of Alzheimer's disease in patients is also disclosed. The method applies detection of specific peptide markers, e.g., using mass spectrometric analysis.

1 . (canceled) 
     
     
         2 . An isolated polypeptide having the amino acid sequence of SEQ ID NO: 17. 
     
     
         3 . A method for assessing the state of Alzheimer's disease in a subject, wherein the method comprises detecting in a sample from the subject at least one polypeptide from each of the following groups:
 a) a polypeptide having an amino acid sequence selected from the group consisting of SEQ ID NO: 7, 8, 9, 10, 11, 12, 13, 14, 15, and 16;   b) a polypeptide having the amino acid sequence selected from the group consisting of SEQ ID NO: 3, 4, 5, and 6; and   c) a polypeptide having the amino acid sequence of SEQ ID NO: 17.   
     
     
         4 . The method of  claim 3 , wherein the method further comprises contacting the sample with an antibody that specifically binds one of the polypeptides. 
     
     
         5 . The method of  claim 3 , wherein at least one polypeptide is detected by SELDI-TOF MS. 
     
     
         6 . The method of  claim 3 , wherein the method is performed on at least two samples from the subject. 
     
     
         7 . The method of  claim 3 , wherein the sample is CSF, blood, serum, plasma, urine, seminal plasma, nipple fluid, or cell extract. 
     
     
         8 . The method of  claim 3 , wherein the polypeptides are detected in one sample from the subject. 
     
     
         9 . A method for assessing the state of Alzheimer's disease in a subject, wherein the method comprises detecting in a sample from the subject at least three distinct polypeptides, wherein a first polypeptide is selected from the group consisting of SEQ ID NO: 3, 4, 5, 6, 7 and 17;
 and wherein a second polypeptide and a third polypeptide are selected from the group consisting of:   a) a polypeptide having the amino acid sequence selected from the group consisting SEQ ID NO: 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, or 17;   b) a human cystatin C;   c) a human beta-2-microglobulin;   d) a 7.7 kD homologue of human myoglobin;   e) neurosecretory protein VGF;   f) a fragment of at least 5 amino acids of human cystatin C;   g) a fragment of at least 5 amino acids of human beta-2-microglobulin;   h) a fragment of at least 5 amino acids of the 7.7 kD homologue of human myoglobin; and   i) a fragment of at least 5 amino acids of neurosecretory protein VGF.   
     
     
         10 . The method of  claim 9 , wherein the method further comprises contacting the sample with an antibody that specifically binds one of the polypeptides. 
     
     
         11 . The method of  claim 9 , wherein at least one polypeptide is detected by SELDI-TOF MS. 
     
     
         12 . The method of  claim 9 , wherein the method is performed on at least two samples from the subject. 
     
     
         13 . The method of  claim 9 , wherein the sample is CSF, blood, serum, plasma, urine, seminal plasma, nipple fluid, or cell extract. 
     
     
         14 . The method of  claim 9 , wherein the polypeptides are detected in one sample from the subject. 
     
     
         15 . The method of  claim 9 , wherein the method comprises detecting at least four distinct polypeptides, wherein a fourth polypeptide is selected from the group consisting of:
 a) a polypeptide having the amino acid sequence selected from the group consisting SEQ ID NO: 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, or 17;   b) a human cystatin C;   c) a human beta-2-microglobulin;   d) a 7.7 kD homologue of human myoglobin;   e) neurosecretory protein VGF;   f) a fragment of at least 5 amino acids of human cystatin C;   g) a fragment of at least 5 amino acids of human beta-2-microglobulin;   h) a fragment of at least 5 amino acids of the 7.7 kD homologue of human myoglobin; and   i) a fragment of at least 5 amino acids of neurosecretory protein VGF.   
     
     
         16 . The method of  claim 15 , wherein the polypeptides are detected in one sample from the subject. 
     
     
         17 . The method of  claim 15 , wherein the method comprises detecting at least five distinct polypeptides, wherein a fifth polypeptide is selected from the group consisting of:
 a) a polypeptide having the amino acid sequence selected from the group consisting SEQ ID NO: 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, or 17;   b) a human cystatin C;   c) a human beta-2-microglobulin;   d) a 7.7 kD homologue of human myoglobin;   e) neurosecretory protein VGF;   f) a fragment of at least 5 amino acids of human cystatin C;   g) a fragment of at least 5 amino acids of human beta-2-microglobulin;   h) a fragment of at least 5 amino acids of the 7.7 kD homologue of human myoglobin; and   i) a fragment of at least 5 amino acids of neurosecretory protein VGF.   
     
     
         18 . The method of  claim 17 , wherein the polypeptides are detected in one sample from the subject.