Methods of determining levels of free amino acids and dipeptides and diagnosing alzheimer's disease

Abstract

Provided herein are methods of diagnosing Alzheimer's disease (“AD”) based on characteristic changes of the levels of certain free amino acids or dipeptides (collectively termed as “AD diagnosis markers”) in the body fluid sample of an individual, carnosine synthesis activities in the plasma, and dopamine synthesis activities in the plasma. Also provided are methods of simultaneously determining the levels of at least two free amino acids or dipeptides in the biological fluid sample of an individual.

What is claimed is: 
     
         1 . A method of diagnosing Alzheimer's disease (“AD”) in an individual, comprising:
 a) comparing the level of at least one AD diagnosis marker in a biological fluid sample from the individual with a reference level, and 
 b) determining whether the individual has AD based on a characteristic change in the level of at least one AD diagnosis biomarker, 
 wherein the AD diagnosis marker is a free amino acid or dipeptide selected from the group consisting of: an imidazole-containing free amino acid or dipeptide having antioxidant properties, an aromatic-containing free amino acid that is a neurotransmitter, a free amino acid or dipeptide associated with urea metabolism or detoxification and NO formation, a glutamate-derived free amino acid or dipeptide, and an asparate or serine-derived free amino acid. 
 
     
     
         2 . The method of  claim 1 , wherein the AD diagnosis marker is a free amino acid or dipeptide selected from the group consisting of: histidine, 1-methyl-histidine, 3-methyl-histidine, carnosine, anserine, tryptophan, phenylalanine, tyrosine, dopamine, DOPA, arginine, citrulline, and ornithine. 
     
     
         3 . The method of  claim 1 , wherein at least one AD diagnosis marker is an imidazole-containing free amino acid or dipeptide having antioxidant properties. 
     
     
         4 . The method of  claim 3 , wherein the imidazole-containing free amino acid or dipeptide is carnosine. 
     
     
         5 . The method of  claim 1 , wherein at least one AD diagnosis marker is an aromatic-containing free amino acid that is a neurotransmitter. 
     
     
         6 . The method of  claim 5 , wherein the aromatic-containing free amino acid is dopamine. 
     
     
         7 . The method of  claim 6 , wherein the aromatic-containing free amino acid is DOPA. 
     
     
         8 . The method of  claim 1 , wherein at least one AD diagnosis marker is an imidazole-containing free amino acid or dipeptide having antioxidant properties and at least one AD diagnosis marker is an aromatic-containing free amino acid. 
     
     
         9 . The method of  claim 1 , wherein at least one AD diagnosis marker is a glutamate-derived free amino acid or dipeptide. 
     
     
         10 . The method of  claim 1 , wherein at least one AD diagnosis marker is an imidazole-containing free amino acid or dipeptide having antioxidant properties, at least one AD diagnosis marker is an aromatic-containing free amino acid, and at least one AD diagnosis marker is a glutamate-derived free amino acid or dipeptide. 
     
     
         11 . The method of any of  claim 1 , comprising comparing the levels of at least two AD diagnosis markers in the individual with reference levels. 
     
     
         12 . The method of  claim 11 , comprising comparing the levels of at least five AD diagnosis markers in the individual with reference levels. 
     
     
         13 . The method of  claim 12 , comprising comparing the levels of at least ten AD diagnosis markers in the individual with reference levels. 
     
     
         14 . A method of diagnosing AD in an individual, comprising:
 a) comparing the CSF level of at least one AD diagnosis marker from the individual with a reference level, and   b) determining whether the individual has AD based on a characteristic change in the CSF level of at least one AD diagnosis biomarker,   wherein the AD diagnosis marker is any of Group 1 or Group 2 AD diagnosis markers.   
     
     
         15 . The method of  claim 14 , wherein a decrease in the CSF level of at least one of Group 1 AD diagnosis markers is indicative of AD. 
     
     
         16 . The method of  claim 14 , wherein an increase in the CSF level of at least one of Group 2 AD diagnosis markers is indicative of AD. 
     
     
         17 . The method of  claim 16 , wherein a decrease in the CSF level of at least one Group 1 AD diagnosis marker and an increase in the CSF level of at least one Group 2 AD diagnosis marker is indicative of AD. 
     
     
         18 . A method of diagnosing AD in an individual, comprising:
 a) comparing the plasma level of at least one AD diagnosis marker from the individual with a reference level, and   b) determining whether the individual has AD based on a characteristic change in the plasma level of at least one AD diagnosis biomarker,   wherein the AD diagnosis marker is any of Group 3 or Group 4 AD diagnosis markers.   
     
     
         19 . The method of  claim 18 , wherein a decrease in the plasma level of at least one of Group 3 AD diagnosis markers is indicative of AD. 
     
     
         20 . The method of  claim 18 , wherein an increase in the plasma level of at least one of Group 4 AD diagnosis markers is indicative of AD.