METHODS AND COMPOSITIONS FOR THE DIAGNOSIS AND PROGNOSIS OF ALZHEIMER'S DISEASE

• US 20120142548A1
• Filed: 04/15/2010
• Published: 06/07/2012
• Est. Priority Date: 04/15/2009
• Status: Active Grant

• Current Assignee: Northern Bank Limited (Danske Bank A/S)
• Original Assignee: Randox Laboratories Limited
• Inventors: Corsi, Massimiliano, Fitzgerald, Stephen P., Lamont, John V., Innocenzi, Paul
• Granted Patent: US 9,726,678 B2
• Time in Patent Office: Days
• US Class Current: 506/9
• CPC Class Codes: G01N 2800/2821 Alzheimer
• CPC Class Codes: G01N 33/6896 Neurological disorders, e.g. Alzheimer's disease

Abstract

The invention relates to methods of diagnosing Alzheimer'"'"'s disease (AD) in a subject and methods of determining the prognosis in patients with AD. The adhesion molecules P-selectin and L-selectin are described for the first time for use as biomarkers to aid in the diagnosis of AD. The invention further describes the use of one or more of L-selectin, MCP-1, IL-1α, IL-8 and IFN-γ to aid in the prognosis of either accelerated cognitive decline (ACD) or slow cognitive decline (SCD) in patients with AD.

Claims

1. A method of diagnosis of Alzheimer'"'"'s disease (AD) comprising:

obtaining an in vitro sample of a peripheral biological fluid from a person suspected of having AD;

measuring the concentration of at least one of P-selectin and L-selectin in the in vitro sample, wherein measuring the concentration of at least one P-selectin and L-selectin comprises probing the in vitro sample using at least one probe for P-selectin and/or L-selectin; and

providing the measured concentration of the at least one P-selectin and L-selectin in the in vitro sample, wherein a decrease in the measured concentration of at least one of P-selectin and L-selectin in the in vitro sample compared to the concentration of at least one of P-selectin and L-selectin in a control sample is indicative of AD.

2. The method according to claim 1, further comprising the determination of the concentration of one or more known biomarkers of AD in the in vitro sample wherein an increase in the concentration of the one or more known biomarkers compared to a control sample in combination with a decrease of the at least one of P-selectin and L-selectin compared to a control sample is indicative of AD.

3. The method of claim 2, wherein the known biomarkers of AD are MCP-1, IL-1α

, IL-1β

, IL-8, IFN-γ and

VEGF.

13. The method of claim 1, wherein the peripheral biological fluid is serum or plasma.

4-12. -12. (canceled)

14. A method of diagnosis of accelerated cognitive decline (ACD) or slow cognitive decline (SCD) in a patient with Alzheimer'"'"'s disease (AD) comprising:

obtaining an in vitro sample of a peripheral biological fluid from a person suspected of having AD;

measuring the concentration of at least one of L-selectin, MCP-1, IL-1α

, IL-8 and IFN-γ

in the in vitro sample wherein measuring the concentration of the at least one L-selectin, MCP-1, IL-1α

, IL-8 and IFN-γ

in the in vitro sample comprises probing the in vitro sample using at least one probe for L-selectin, MCP-1, IL-1α

, IL-8 and/or IFN-γ

; and

providing the measured concentration of the at least one L-selectin, MCP-1, IL-1α

, IL-8 and/or IFN-γ

in the in vitro sample, wherein an increase in the measured concentration of the at least one of MCP-1, IL-1α

, IL-8 and IFN-γ

in the in vitro sample compared to a control sample is indicative of SCD and wherein a decrease in the measured concentration of L-selectin in the in vitro sample compared to the control sample is indicative of ACD.

15. The method of claim 14, wherein the peripheral biological fluid is serum or plasma.

16. Use of at least one of L-selectin, MCP-1, IL-1α

, IL-8 and IFN-γ

as a biomarker in the diagnosis of accelerated cognitive decline (ACD) or slow cognitive decline (SCD) in a patient suffering from Alzheimer'"'"'s disease (AD).

17. Use of at least one of L-selectin, MCP-1, IL-1α

, IL-8 and IFN-γ

as a complementary biomarker in the diagnosis of accelerated cognitive decline (ACD) or slow cognitive decline (SCD) in a patient suffering from Alzheimer'"'"'s disease.

18. Use of at least one of P-selectin and L-selectin as a biomarker in the diagnosis of Alzheimer'"'"'s disease.

19. A kit for use in the diagnosis of Alzheimer'"'"'s disease comprising at least one analyte-specific probe for P-selectin and/or L-selectin together with at least one probe for one or more known biomarkers of Alzheimer'"'"'s disease.

20. A kit according to claim 19, wherein the at least one analyte-specific probe is an antibody.

21. A kit for use in the diagnosis of Alzheimer'"'"'s disease comprising at least one analyte-specific probe for P-selectin and/or L-selectin.

22. A kit according to claim 21, wherein the at least one analyte-specific probe is an antibody.

23. A kit for use in the diagnosis of slow cognitive decline (SCD) or accelerated cognitive decline (ACD) in a patient suffering from Alzheimer'"'"'s disease comprising at least one analyte-specific probe for one or more biomarkers selected from L-selectin, MCP-1, IL-1α

, IL-8 and IFN-γ

.

24. A kit according to claim 23, wherein the at least one analyte-specific probe is an antibody.