Antemortem diagnostic test for Alzheimer's disease

A method of screening for Alzheimer's disease in a human, comprising the steps of:

• a. determining a ratio of the concentration of a neuronal membrane phospholipid to the concentration of its metabolite, the ratio selected from the group consisting of:
• the ratio of the concentration of phosphatidylcholine to the concentration of a phosphatidylcholine metabolite, or the ratio of the concentration of phosphatidylethanolamine to the concentration of a phosphatidylethanolamine metabolite, in a sample of cerebrospinal fluid obtained from the human, thereby obtaining a test ratio;
• and
• b. comparing the test ratio with a control ratio, wherein the control ratio is the same ratio determined in a) in a sample of cerebrospinal fluid from a human who does not currently demonstrate clinical manifestation of neurodegenerative disease,
• wherein a test ratio greater than the control ratio is indicative of Alzheimer's disease.

A method of screening for Alzheimer's disease in a human, comprising the steps of:

• a. collecting a sample of cerebrospinal fluid from the human;
• b. determining a test value selected from the group consisting of:
• (i) the concentration of a neuronal phospholipid selected from the group consisting of phosphatidylcholine and phosphatidylethanolamine;
• (ii) the concentration of a neuronal phospholipid metabolite selected from the group consisting of metabolites of phosphatidylcholine and metabolites of phosphatidylethanolamine;
• and
• (iii) a ratio of the concentration of a neuronal membrane phospholipid to the concentration of its metabolite, the ratio being selected from the group consisting of:
• the ratio of the concentration of phosphatidylcholine to the concentration of a phosphatidylcholine metabolite, or the ratio of the concentration of phosphatidylethanolamine to the concentration of a phosphatidylethanolamine metabolite in the sample;
• and
• c. comparing the test value with a control value, wherein the control value is the same concentration or ratio determined in b) in a sample of cerebrospinal fluid from a human who does not currently demonstrate clinical manifestation of neurodegenerative disease,
• wherein a test value greater than the control value is indicative of Alzheimer's disease.

A method of predicting the likelihood that a human will develop Alzheimer's disease, comprising the steps of:

• a. collecting a sample of cerebrospinal fluid from the human;
• b. determining a test value selected from the group consisting of:
• (i) the concentration of a neuronal phospholipid selected from the group consisting of phosphatidylcholine and phosphatidylethanolamine;
• (ii) the concentration of a neuronal phospholipid metabolite selected from the group consisting of metabolites of phosphatidylcholine and metabolites of phosphatidylethanolamine;
• or
• (iii) a ratio of the concentration of a neuronal membrane phospholipid to the concentration of its metabolite, the ratio being selected from the group consisting of:
• the ratio of the concentration of phosphatidylcholine to the concentration of a phosphatidylcholine metabolite, or the ratio of the concentration of phosphatidylethanolamine to the concentration of a phosphatidylethanolamine metabolite in the sample;
• and
• c. comparing the test value with a control value, wherein the control value is the same concentration or ratio determined in b) in a sample of cerebrospinal fluid from a human who does not currently demonstrate clinical manifestation of neurodegenerative disease,
• wherein a test value greater than the control value is indicative of the likelihood of development of Alzheimer's disease.

A method of following the course of Alzheimer's disease in a human, comprising the steps of:

• a. determining the concentration of a neuronal phospholipid selected from the group consisting of phosphatidylcholine and phosphatidylethanolamine, or the concentration of a neuronal phospholipid metabolite selected from the group consisting of metabolites of phosphatidylcholine and metabolites of phosphatidylethanolamine, in a series of correlating samples of cerebrospinal fluids taken from the human at regular intervals after diagnosis of probable Alzheimer's disease, thereby obtaining a series of test values;
• and
• b. comparing the test values with a control value, wherein the control value is the concentration of the neuronal phospholipid or the neuronal phospholipid in a sample of cerebrospinal fluid from a human who does not currently demonstrate clinical manifestation of neurodegenerative disease,
• wherein an increase in the deviation of the concentration of a first test value from the control value, as compared with the deviation of the concentration of a second test value from the subsequent interval from the control value, is indicative of progression of Alzheimer's disease.

A method of following the course of Alzheimer's disease in a human, comprising the steps of:

• a. determining the ratio of the concentration of a neuronal membrane phospholipid to the concentration of its metabolite, the ratio selected from the group consisting of:
• the ratio of the concentration of phosphatidylcholine to the concentration of a phosphatidylcholine metabolite, and the ratio of the concentration of phosphatidylethanolamine to a phosphatidylethanolamine metabolite, in a series of correlating samples of cerebrospinal fluids taken from the human at regular intervals after diagnosis of probable Alzheimer's disease, thereby obtaining a series of test ratio values, and
• b. comparing the test ratio values with a control ratio, wherein the control ratio is the same ratio determined in a) in a sample of cerebrospinal fluid from a human who does not currently demonstrate clinical manifestation of neurodegenerative disease,
• wherein an increase in the deviation of a first test ratio value from the control ratio value, as compared with the deviation of a second test ratio value from the subsequent interval from the control ratio value, is indicative of progression of Alzheimer's disease.

A method of screening for Alzheimer's disease in a human, comprising the steps of:

• a. determining the concentration of glycerophosphocholine in a sample of cerebrospinal fluid obtained from the human, thereby obtaining a test value;
• and
• b. comparing the test value with a control value, wherein the control value is the concentration of glycerophosphocholine from a sample of cerebrospinal fluid from a human who does not currently demonstrate clinical manifestation of neurodegenerative disease,
• wherein a test value greater than the control value is indicative of Alzheimer's disease.

A method of diagnosing Alzheimer's disease in a human, comprising the steps of:

• a. determining the ratio of the concentration of phosphatidylcholine to the concentration of glycerophosphocholine in a sample of cerebrospinal fluid obtained from the human, thereby obtaining a test ratio;
• and
• b. comparing the test ratio with a control ratio, wherein the control ratio is the ratio of the concentration of phosphatidylcholine to the concentration of glycerophosphocholine from a sample of cerebrospinal fluid from a human who does not currently demonstrate clinical manifestation of neurodegenerative disease,
• wherein a test ratio greater than the control ratio is indicative of Alzheimer's disease.

A method of diagnosing Alzheimer's disease in a human, comprising the steps of:

• a. collecting a sample of cerebrospinal fluid from the human;
• b. determining a test value selected from the group consisting of:
• the concentration of glycerophosphocholine, and the ratio of phosphatidylcholine to glycerophosphocholine in the sample;
• and
• c. comparing the test value with a control value, wherein the control value is the corresponding test value from a sample of cerebrospinal fluid from a human who does not currently demonstrate clinical manifestation of disease, wherein a test value greater than the control value is indicative of Alzheimer's disease.