Methods of diagnosing Alzheimer's disease

• US 7,897,361 B2
• Filed: 09/29/2005
• Issued: 03/01/2011
• Est. Priority Date: 09/29/2004
• Status: Active Grant

• Current Assignee: Proteome Sciences, PLC, Kings College London (University of London)
• Original Assignee: Kings College London (University of London)
• Inventors: Ward, Malcolm, Kienle, Stefan, Schaefer, Juergen, Lovestone, Simon, Prefot, Petra, Byers, Helen, Lynham, Stephen, Hye, Abdul, Baumann, Christian, Kuhn, Karsten, Prinz, Thorsten, Westbrook, Jules, Joubert, Richard
• Primary Examiner(s): Chernyshev; Olga N
• Application Number:
  US11/664,076
• Publication Number:
  US 20080070995A1
• Time in Patent Office: 1,979 Days
• Field of Search: None
• US Class Current: 435/7.92
• CPC Class Codes: A61P 25/28 for treating neurodegenerative disorders of the central nervous system, e.g. nootropic agents, cognition enhancers, drugs for treating Alzheimer's disease or other forms of dementia
• CPC Class Codes: G01N 2800/2821 Alzheimer
• CPC Class Codes: G01N 2800/52 Predicting or monitoring the response to treatment, e.g. for selection of therapy based on assay results in personalised medicine; Prognosis
• CPC Class Codes: G01N 33/6896 Neurological disorders, e.g. Alzheimer's disease

Abstract

Methods and compositions relating to Alzheimer'"'"'s disease are provided. Specifically, proteins that are differentially expressed in the Alzheimer'"'"'s disease state relative to their expression in the normal state are provided. Proteins associated with Alzheimer'"'"'s disease are identified and described. Methods of diagnosis of Alzheimer'"'"'s disease using the differentially expressed proteins are also provided, as are methods for the identification and therapeutic use of compounds for the prevention and treatment of Alzheimer'"'"'s disease.

Claims

1. A method of diagnosing Alzheimer'"'"'s disease in a subject, the method comprising detecting a differentially expressed protein, said protein being clusterin precursor protein (Swiss-PROT Accession number (SPN) P10909), in a sample of blood or plasma from said subject, wherein a decrease in the expression of said clusterin precursor protein compared to the expression of said protein in a control subject is indicative of Alzheimer'"'"'s disease in the subject undergoing diagnosis.

2. A method according to claim 1, wherein the clusterin precursor protein is detected in the sample using (i) an antibody specific to said clusterin precursor protein;

(ii) via detection of an autoantibody specific to said clusterin precursor protein, or by mass spectrometry.

3. A method according to claim 1, wherein the clusterin precursor protein is detected using 2D gel electrophoresis.

4. A method according to claim 2 wherein the sample is immobilised on a solid support.

5. A method according to claim 1, wherein said sample is a blood sample.

6. A method according to claim 1, further comprising detecting said clusterin precursor protein in combination with detection of an increase or decrease of the expression level of at least one other differentially expressed protein biomarker of Alzheimer'"'"'s disease selected from the group consisting of the following proteins or a fragment thereof:

apolipoprotein A-N precursor (SPN P06727), as determined by an increase in the expression thereof, apolipoprotein C-III precursor (SPN P02656), as determined by an increase in the expression thereof, transthyretin (SPN P02766), as determined by an increase in the expression thereof, galectin 7 (SPN P47929), as determined by an increase in the expression thereof, complement C4 precursor (SPN P01028), as determined by an increase in the expression thereof, complement factor H (SPN P08603), as determined by an increase in the expression thereof, S100 calcium binding protein or ceruloplasmin precursor (SPN P00450), as determined by an increase in the expression thereof, histone H2B. a/g/h/k/l (SPN P62807), as determined by a decrease in the expression thereof, Ig lambda chain C region (SPN P01842), as determined by an increase in the expression thereof, inter-alpha-trypsin inhibitor heavy chain H4 precursor (SPN Q14624), as determined by an increase in the expression thereof, complement C3 precursor (SPN P01024), as determined by a decrease in the expression thereof, gamma/beta actin (SPN P63261), as determined by an increase in the expression thereof, haptoglobin precursor (SPN P00738), as determined by an increase in the expression thereof, alpha-2-macroglobulin (SPN P01023), as determined by an increase in the pression thereof and the serum albumin precursor isoform (SPN P02768), as determined by an increase in the expression thereof, said determination(s) being in comparison to the expression of the same protein(s) in a control subject.

7. A method according to claim 6 which comprises detecting more than one differentially expressed protein.

8. A method according to claim 7 which comprises detecting four or more differentially expressed proteins.