BIOMARKERS OF MILD COGNITIVE IMPAIRMENT AND ALZHEIMER'S DISEASE

• US 20110104724A1
• Filed: 11/08/2010
• Published: 05/05/2011
• Est. Priority Date: 07/25/2006
• Status: Abandoned Application

• Current Assignee: University Of Kentucky Research Foundation (University of Kentucky)
• Original Assignee: University Of Kentucky Research Foundation (University of Kentucky)
• Inventors: Lovell, Mark A., Lynn, Bert C.
• Application Number:
  US12/941,721
• Publication Number:
  US 20110104724A1
• Time in Patent Office: Days
• US Class Current: 435/7.92
• CPC Class Codes: G01N 2800/2821 Alzheimer
• CPC Class Codes: G01N 33/6896 Neurological disorders, e.g. Alzheimer's disease

Abstract

A method for quantifying a neurodegenerative disorder in a patient that includes obtaining a fluid sample from the subject; measuring a protein biomarker complex in said fluid sample and correlating the measurement with mild cognitive impairment or Alzheimer'"'"'s disease status. The biomarkers include those that comprise at least one of a transthyretin protein and/or a prostaglandin-H2 D-isomerase protein, and at least one second, different protein selected from a transthyretin, prostaglandin-H2 D-isomerase, beta-2-microglobulin, cystatin C, superoxide dismutase [Cu—Zn], plasma retinol-binding protein, phosphatidylethanolamine-binding protein, carbonic anhydrase 2, prostaglandin-H2 D-isomerase, and/or serotransferrin protein;

Claims

1. A method for quantifying a neurodegenerative disorder in a patient, comprising:

(a) obtaining a fluid sample from the subject;

(b) measuring a protein biomarker complex in said fluid sample that comprises;

at least one of a transthyretin protein and/or a prostaglandin-H2 D-isomerase protein, and

at least one second, different protein selected from a transthyretin, prostaglandin-H2 D-isomerase, beta-2-microglobulin, cystatin C, superoxide dismutase [Cu—

Zn], plasma retinol-binding protein, phosphatidylethanolamine-binding protein, carbonic anhydrase 2, prostaglandin-H2 D-isomerase, and/or serotransferrin protein; and

(c) correlating the measurement with mild cognitive impairment or Alzheimer'"'"'s disease status.

2. The method of claim 1, wherein the protein biomarker complex comprises transthyretin and prostaglandin-H2 D-isomerase.

3. The method of claim 1, wherein said measuring step comprises trapping by enzyme linked immunosorbent assay (ELISA) at least one of transthyretin and/or prostaglandin-H2 D-isomerase;

and

probing for a second, different protein selected from the group consisting of at least one of transthyretin, prostaglandin-H2 D-isomerase, beta-2-microglobulin, cystatin C, superoxide dismutase [Cu—

Zn], plasma retinol-binding protein, phosphatidylethanolamine-binding protein, carbonic anhydrase 2, prostaglandin-H2 D-isomerase, and/or serotransferrin is identified by probing the trapped protein.

4. The method of claim 3, wherein the measuring step comprises trapping for a transthyretin protein.

5. The method of claim 4, wherein the measuring step further comprises, after trapping for the transthyretin protein, probing for at least one of prostaglandin-H2 D-isomerase, beta-2-microglobulin, cystatin C, superoxide dismutase [Cu—

Zn], plasma retinol-binding protein, phosphatidylethanolamine-binding protein, carbonic anhydrase 2, prostaglandin-H2 D-isomerase, and/or serotransferrin.

6. The method of claim 4, wherein the measuring step further comprises, after trapping for a transthyretin protein, probing for a prostaglandin-H2 D-isomerase protein.

7. The method of claim 1, wherein the correlating step comprises comparing an amount of said protein biomarker complex with a reference value in a control sample.

8. The method of claim 7, wherein the control sample is from a normal individual.

9. The method of claim 8, wherein the control sample is from a previous sample taken from a patient.

10. The method of claim 9, further comprising comparing the control sample with the fluid sample of the subject to determine the progression of the mild cognitive impairment or the Alzheimer'"'"'s disease.

11. The method of claim 1, wherein the fluid sample is cerebrospinal fluid.

12. The method of claim 1, wherein the sample from the subject is collected via a spinal tap.

13. A method of monitoring the progression of a neurological disorder, comprising:

comparing a first measured level of a biomarker complex with a reference level of said biomarker complex, the complex comprising at least one of a transthyretin protein and/or a prostaglandin-H2 D-isomerase protein, and at least one second, different protein selected from a transthyretin, prostaglandin-H2 D-isomerase, beta-2-microglobulin, cystatin C, superoxide dismutase [Cu—

Zn], plasma retinol-binding protein, phosphatidylethanolamine-binding protein, carbonic anhydrase 2, prostaglandin-H2 D-isomerase, and/or serotransferrin protein; and

after allowing a period of time to pass, comparing a second measured level of the biomarker complex to said reference level and/or to said first measured level of the biomarker complex; and

determining the progression of the disease based on the first and second measured level of said biomarker complex.

14. The method of claim 13, wherein the biomarker complex comprises a transthyretin protein and a prostaglandin-H2 D-isomerase protein.

15. The method of claim 13, wherein the neurological disorder is mild cognitive impairment.

16. The method of claim 13, wherein the neurological disorder is Alzheimer'"'"'s disease.

17. The method of claim 13, wherein the biomarker is measured by enzyme linked immunosorbent assay (ELISA).

18. A diagnostic kit for quantifying Alzheimer'"'"'s disease status, comprising:

a solid support coated with an antibody to capture at lease one of a protein complex selected from prostaglandin-D-synthase and/or transthyretin; and

a second primary antibody to recognize the second component of the protein complex, the second component selected from a transthyretin, prostaglandin-H2 D-isomerase, beta-2-microglobulin, cystatin C, superoxide dismutase [Cu—

Zn], plasma retinol-binding protein, phosphatidylethanolamine-binding protein, carbonic anhydrase 2, prostaglandin-H2 D-isomerase, and/or serotransferrin protein.

19. The kit of claim 18, wherein the solid support is a 96 well polystyrene microtiter plate.

20. The kit of claim 18, wherein the solid support is coated with anti-prostaglandin-D-synthase for protein capture.

21. The kit of claim 18, wherein said second primary antibody is anti-human transthyretin.

22. The kit of claim 18, further comprising TMB color reagent and stopping solution.