Methods for aiding in the diagnosis of alzheimer's disease by measuring amyloid-β peptide (X->41) and tau
This invention provides methods useful in aiding in the diagnosis of Alzheimer's disease. The methods involve measuring the amount of amyloid-β peptide (x-≧41) in the cerebrospinal fluid of a patient. High levels of the peptide generally are inconsistent with a diagnosis of Alzheimer's. Low levels of the peptide are consistent with the disease and, with other tests, can provide a positive diagnosis. Other methods involve measuring the amounts of both Aβ(x-≧41) and tau. Low levels of Aβ(x-≧41) and high levels of tau are a positive indicator of Alzheimer's disease, while high levels of Aβ(x-≧41) and low levels of tau are a negative indication of Alzheimer's disease.
1. A method for diagnosing probable Alzheimer's disease in a patient, the method comprising:
measuring the amount of one or more soluble Aβ(x-≧41) in a cerebrospinal fluid sample;
comparing the measured amount of the soluble Aβ(x-≧41) with a predetermined indicator value of the Aβ(x-≧41);
measuring the amount of tau in a cerebrospinal fluid sample;
comparing the measured amount of tau with a predetermined indicator value of tau; and
assessing patient status based on a difference between the measured amounts and predetermined indicator values, wherein a measured amount at or below the Aβ(x-≧41) indicator value and at or above the tau indicator value provides a positive indication in the diagnosis of probable Alzheimer's disease, and wherein a measured amount above the Aβ(x-≧41) indicator value and below the tau indicator value provides a negative indication in the diagnosis of probable Alzheimer's disease.
2. The method of claim 1 , wherein Aβ(x-≧41) is Aβ 1-42 or Aβ 6-42 .
3. The method of claim 1 , wherein the amount of the soluble Aβ(x-≧41) is measured by:
capturing the soluble Aβ(x-≧41) from the sample on a solid phase with a first antibody or antibody fragment specific for an epitope within a junction region of Aβ disposed between amino acids 13-26; and
detecting capture of the soluble Aβ(x-≧41) using a second antibody or antibody fragment specific for Aβ(x-≧41).
4. The method of claim 3 , wherein the detecting step comprises detecting binding between the second antibody or antibody fragment and Aβ(x-≧41) using a third labeled antibody or antibody fragment that recognizes the second antibody or antibody fragment but not the first antibody or antibody fragment.
5. The method of claim 3 , wherein the first antibody or antibody fragment has the specificity of an antibody raised against Aβ 13-28 .
6. The method of claim 3 , wherein the second antibody or antibody fragment has the specificity of an antibody raised against amino acids 33-42 of Aβ.
7. The method of claim 1 , wherein the amount of the soluble Aβ(x-≧41) is measured by:
capturing the soluble Aβ(x-≧41) from the sample on a solid phase with a first antibody or antibody fragment specific for Aβ(x-≧41); and
detecting capture of the soluble Aβ(x-≧41) using a second antibody or antibody fragment that recognizes Aβ.
8. The method of claim 7 , wherein the detecting step comprises detecting binding between the second antibody or antibody fragment and Aβ(x-≧41) using a third labeled antibody or antibody fragment that recognizes the second antibody or antibody fragment but not the first antibody or antibody fragment.
9. The method of claim 7 , wherein the first antibody or antibody fragment has the specificity of an antibody raised against amino acids 33-42 of Aβ.
10. The method of claim 7 , wherein the second antibody or antibody fragment is specific for an epitope within a junction region of Aβdisposed between amino acids 13-26.
11. The method of claim 1 , wherein the amount of the soluble Aβ(x-≧41) is measured by:
capturing the soluble Aβ(x-≧41) from the sample on a solid phase with a first antibody or antibody fragment specific for Aβ; and
detecting capture of the soluble Aβ(x-≧41) using a second antibody or antibody fragment specific for Aβ(x-≧41).
12. The method of claim 11 , wherein the detecting step comprises detecting binding between the second antibody or antibody fragment and Aβ(x-≧41) using a third labeled antibody or antibody fragment that recognizes the second antibody or antibody fragment but not the first antibody or antibody fragment.
13. The method of claim 11 , wherein the second antibody or antibody fragment has the specificity of an antibody raised against amino acids 33-42 of Aβ.
14. The method of claim 4 , wherein the label is an enzymatic label.
15. The method of claim 6 , wherein the first antibody or antibody fragment has the specificity of an antibody raised against Aβ 13-28 .
16. The method of claim 8 , wherein the label is an enzymatic label.
17. The method of claim 10 , wherein the second antibody or antibody fragment has the specificity of an antibody raised against Aβ 13-28 .
18. The method of claim 12 , wherein the label is an enzymatic label.