Biomarkers for alzheimer's disease
The present invention provides protein-based biomarkers and biomarker combinations that are useful in qualifying Alzheimer's disease status in a patient. In particular, the biomarkers of this invention are useful to classify a subject sample as Alzheimer's or non-Alzheimer's dementia or normal. The biomarkers can be detected by SELDI mass spectrometry. In addition, the invention provides appropriate treatment interventions and methods for measuring response to treatment. Certain biomarkers of the invention may also be suitable for employment as radio-labeled ligands in non-invasive imaging techniques such as Positron Emission Tomography (PET).
1. A method for qualifying Alzheimer's disease status in a subject comprising:
(a). measuring at least one biomarker in a CSF sample from the subject, wherein said at least one biomarker consists of residues 35-121 of SEQ ID NO:4;
(b). comparing the level of the biomarker in said
subject to a diagnostic cut-off level; and
(c). correlating the measurement with Alzheimer's disease status, wherein elevated levels of the biomarker in said CSF sample relative to said diagnostic cut-off level are indicative of an increased likelihood of Alzheimer's disease in said subject.
2. The method of claim 1 , wherein said at least one biomarker is a single biomarker, and.
3. The method of claim 1 , further comprising measuring Pancreatic ribonuclease.
4. The method of claim 1 , further comprising measuring Apolipoprotein C-I.
5. The method of claim 1 , further comprising measuring Cystatin C.
6. The method of claim 1 , further comprising measuring at least each of the following biomarkers: Pancreatic ribonuclease, C3a des-Arg, Apolipoprotein C-I and Cystatin C.
7. The method of claim 1 , wherein the at least one biomarker is measured by a means of detection other than by mass.
8. The method of claim 7 , wherein the at least one biomarker is measured by immunoassay.
9. The method of claim 1 or 2 , wherein the at least one biomarker is measured by immunoassay.
10. The method of claim 1 or 2 , wherein the at least one biomarker is measured by capturing the biomarker on an adsorbent surface of a SELDI probe and detecting the captured biomarkers by laser desorption-ionization mass spectrometry.
11. The method of claim 10 , wherein the adsorbent is a cation exchange adsorbent.
12. The method of claim 10 , wherein the adsorbent is a biospecific adsorbent.
13. The method of claim 10 , wherein the adsorbent is a hydrophobic adsorbent.
14. The method of claim 1 or 2 , wherein the correlating is performed by a software classification algorithm.
15. The method of claim 1 or 2 , further comprising (d) managing subject treatment based on the status.
16. The method of claim 15 , further comprising:
(e) measuring the at least one biomarker after subject management.
17. The method of claim 1 or 2 , wherein Alzheimer's disease status is selected from Alzheimer's disease and non-dementia, wherein decreased levels of the biomarker in said CSF sample relative to said diagnostic cut-off level are indicative of non-dementia.
18. The method of claim 17 , wherein, if the measurement correlates with Alzheimer's disease, then managing subject treatment comprises administering a choline esterase inhibitor to the subject.
19. The method of claim 1 or 2 , wherein Alzheimer's disease status is selected from Alzheimer's disease, non-dementia, and non-Alzheimer's dementia, wherein decreased levels of the biomarker in said CSF sample relative to said diagnostic cut-off level are indicative of non-dementia or non-Alzheimer's dementia.
20. The method of claim 1 or 2 , wherein Alzheimer's disease status is selected from Alzheimer's disease and non-Alzheimer's dementia, wherein decreased levels of the biomarker in said CSF sample relative to said diagnostic cut-off level are indicative non-Alzheimer's dementia.
21. The method of claim 20 wherein non-Alzheimer's dementia is selected from dementia with Lewy bodies and frontotemporal dementia.