Metabolic biomarkers for memory loss
The present invention relates to methods of determining if a subject has an increased risk of suffering from memory impairment. The methods comprise analyzing at least one plasma sample from the subject to determine a value of the subject's metabolite profile and comparing the value of the subject's metabolite profile with the value of a normal metabolite profile. A change in the value of the subject's metabolite profile, over normal values is indicative that the subject has an increased risk of suffering from memory impairment compared to a normal individual.
1. A method of measuring levels of metabolites in a subject, the method comprising obtaining a sample from a subject and determining individual levels of phosphatidylcholine acyl-alkyl C36:4 (PC ae C36:4), decadienyl-L-carnitine (C10:2), phosphatidylcholine diacyl C38:3 (PC aa C38:3), phosphatidylcholine diacyl C34:4 (PC aa C34:4), hydroxyoctadecenoyl-L-carnitine (C18:1-OH), phosphatidylcholine acyl-alkyl C34:0 (PC ae C34:0), hydroxyvaleryl-L-carnitine/methylmalonyl-L-carnitine (C5-OH/C3-DC-M), phosphatidylcholine diacyl C40:5 (PC aa C40:5), phosphatidylcholine diacyl C32:0 (PC aa C32:0), and dodecenoyl-L-carnitine (C12:1).
2. The method of claim 1 , wherein the set of metabolites further comprises one or more metabolites selected from the group consisting of proprionyl-L-carnitine (C3), lysophosphatidylcholine acyl C18:2 (lysoPC a C18:2), phosphatidylcholine diacyl C36:6 (PC aa C36:6), phosphatidylcholine diacyl C38:0 (PC aa C38:0), phosphatidylcholine diacyl C38:6 (PC aa C38:6), phosphatidylcholine diacyl C40:1 (PC aa C40:1), phosphatidylcholine acyl-alkyl C40:6 (PC ae C40:6), hexadecadienyl-L-carnitine (C16:2), Asparagine (Asn), Asymmetric dimethylarginine (ADMA), valeryl-L-carnitine (C5), decenoyl-L-carnitine (C10:1), nonayl-L-carnitine (C9) and phosphatidylcholine acyl-alkyl C42:1 (PC ae C42:1).
3. A method of treating a subject who has an increased risk of memory impairment, the method comprising
a) determining whether the subject has an increased risk of memory impairment by analyzing a set of metabolites from at least one sample from the subject to determine the subject's concentrations of each metabolite in the set of metabolites, and comparing the concentrations of each metabolite in the subject's set of metabolites to concentrations of metabolites from subjects determined to define normal concentrations of each metabolite of the set of metabolites, wherein the subject is determined to have an increased risk of memory impairment when the subject's concentrations of metabolites are altered compared to the normal concentrations of metabolites, and
b) administering a treatment for memory impairment when it is determined that the subject has an increased risk of memory impairment,
wherein the set of metabolites comprises phosphatidylcholine acyl-alkyl C36:4 (PC ae C36:4), decadienyl-L-carnitine (C10:2), phosphatidylcholine diacyl C38:3 (PC aa C38:3), phosphatidylcholine diacyl C34:4 (PC aa C34:4), hydroxyoctadecenoyl-L-carnitine (C18:1-OH), phosphatidylcholine acyl-alkyl C34:0 (PC ae C34:0), hydroxyvaleryl-L-carnitine/methylmalonyl-L-carnitine (C5-OH/C3-DC-M), phosphatidylcholine diacyl C40:5 (PC aa C40:5), phosphatidylcholine diacyl C32:0 (PC aa C32:0), and dodecenoyl-L-carnitine (C12:1), and
wherein the subject's concentrations of metabolites are altered compared to the normal concentrations of metabolites if for at least 8 of the metabolites in the set of metabolites, the subject's concentration of the metabolite is lower as compared to the normal concentration of metabolite.
4. The method of claim 3 , wherein the set of metabolites further comprises one or more metabolites selected from the group consisting of proprionyl-L-carnitine (C3), lysophosphatidylcholine acyl C18:2 (lysoPC a C18:2), phosphatidylcholine diacyl C36:6 (PC aa C36:6), phosphatidylcholine diacyl C38:0 (PC aa C38:0), phosphatidylcholine diacyl C38:6 (PC aa C38:6), phosphatidylcholine diacyl C40:1 (PC aa C40:1), phosphatidylcholine acyl-alkyl C40:6 (PC ae C40:6), hexadecadienyl-L-carnitine (C16:2), Asparagine (Asn), Asymmetric dimethylarginine (ADMA), valeryl-L-carnitine (C5), decenoyl-L-carnitine (C10:1), nonayl-L-carnitine (C9) and phosphatidylcholine acyl-alkyl C42:1 (PC ae C42:1).
5. The method of claim 3 , wherein the normal concentrations of metabolites comprise the subject's concentrations of metabolites prior to the onset of memory impairment.
6. The method of claim 3 , wherein the normal concentrations of metabolites comprise concentrations of metabolites generated from a population of individuals that do not display memory impairment.
7. The method claim 3 , wherein the subject's concentrations of metabolites are altered compared to the normal concentrations of metabolites if for at least 9 of the metabolites in the set of metabolites, the subject's concentration of the metabolite is lower as compared to the normal concentration of metabolite.
8. A method of treating a subject who has an increased risk of memory impairment, the method comprising
a) determining whether the subject has an increased risk of memory impairment by analyzing a set of metabolites from at least one sample from the subject to determine the subject's concentrations of each metabolite in the set of metabolites, and comparing the concentrations of each metabolite in the subject's set of metabolites to concentrations of metabolites from subjects determined to define normal concentrations of each metabolite of the set of metabolites, wherein the subject is determined to have an increased risk of memory impairment when the subject's concentrations of metabolites are altered compared to the normal concentrations of metabolites, and
b) administering a treatment for memory impairment when it is determined that the subject has an increased risk of memory impairment,
wherein the set of metabolites comprises phosphatidylcholine acyl-alkyl C36:4 (PC ae C36:4), decadienyl-L-carnitine (C10:2), phosphatidylcholine diacyl C38:3 (PC aa C38:3), phosphatidylcholine diacyl C34:4 (PC aa C34:4), hydroxyoctadecenoyl-L-carnitine (C18:1-OH), phosphatidylcholine acyl-alkyl C34:0 (PC ae C34:0), hydroxyvaleryl-L-carnitine/methylmalonyl-L-carnitine (C5-OH/C3-DC-M), phosphatidylcholine diacyl C40:5 (PC aa C40:5), phosphatidylcholine diacyl C32:0 (PC aa C32:0), and dodecenoyl-L-carnitine (C12:1), and
wherein the subject's concentrations of metabolites are altered compared to the normal concentrations of metabolites if for at least 8 of the metabolites in the set of metabolites, the ratio of the subject's concentration of the metabolite to the normal concentration of metabolite is less than one.
9. The method of claim 8 , wherein the subject's concentrations of metabolites are altered compared to the normal concentrations of metabolites if for at least 9 of the metabolites in the set of metabolites, the ratio of the subject's concentration of the metabolite to the normal concentration of metabolite is less than one.
10. A method of treating a subject who has an increased risk of memory impairment, the method comprising
a) determining whether the subject has an increased risk of memory impairment by analyzing a set of metabolites from at least one sample from the subject to determine the subject's concentrations of each metabolite in the set of metabolites, and comparing the concentrations of each metabolite in the subject's set of metabolites to concentrations of metabolites from subjects determined to define normal concentrations of each metabolite of the set of metabolites, wherein the subject is determined to have an increased risk of memory impairment when the subject's concentrations of metabolites are altered compared to the normal concentrations of metabolites, and
b) administering a treatment for memory impairment when it is determined that the subject has an increased risk of memory impairment,
wherein the set of metabolites comprises phosphatidylcholine acyl-alkyl C36:4 (PC ae C36:4), decadienyl-L-carnitine (C10:2), phosphatidylcholine diacyl C38:3 (PC aa C38:3), phosphatidylcholine diacyl C34:4 (PC aa C34:4), hydroxyoctadecenoyl-L-carnitine (C18:1-OH), phosphatidylcholine acyl-alkyl C34:0 (PC ae C34:0), hydroxyvaleryl-L-carnitine/methylmalonyl-L-carnitine (C5-OH/C3-DC-M), phosphatidylcholine diacyl C40:5 (PC aa C40:5), phosphatidylcholine diacyl C32:0 (PC aa C32:0), and dodecenoyl-L-carnitine (C12:1), and
wherein the subject's concentrations of metabolites are altered compared to the normal concentrations of metabolites if for at least 8 of the metabolites in the set of metabolites, the log ratio of the subject's concentration of the metabolite to the normal concentration of metabolite is negative.
11. The method of claim 10 , wherein the subject's concentrations of metabolites are altered compared to the normal concentrations of metabolites if for at least 9 of the metabolites in the set of metabolites, the log ratio of the subject's concentration of the metabolite to the normal concentration of metabolite is negative.