Method for aiding diagnosis of Alzheimer's disease
The present invention provides an ex vivo method for aiding the diagnosis of Alzheimer's disease in a patient comprising: (i) determining the number of alleles of ApoE4 in the patient's genome; (ii) determining the combined expression level of at least three platelet proteins in a platelet sample from the patient; and (iii) comparing the resulting value of step (ii) to a control value, wherein the at least three platelet proteins include at least one isoform of alpha-tropomyosin containing exon 1a and at least two platelet proteins selected from monoamine oxidase-B, coagulation factor XIIIa, wild-type GSTO-1 or mutant GSTO-1, wherein a result higher than the control value is indicative of Alzheimer's disease. The invention also provides a solid support comprising one or more ligands of at least one isoform of alpha-tropomyosin containing exon 1a, and one or more ligands of at least two platelet proteins selected from monoamine oxidase-B, coagulation factor XIIIa, wild-type GSTO-1 protein and/or mutant GSTO-1 protein immobilized thereon.
1. An ex vivo method for aiding the diagnosis of Alzheimer's disease in a patient comprising:
(i) determining the number of alleles of apolipoprotein E4 (ApoE4) in the patient's genome using an ApoE4 specific monoclonal antibody that specifically binds an epitope containing residue 112 of ApoE4;
(ii) determining the combined expression level of at least three platelet proteins in a platelet sample obtained from the patient,
wherein the at least three platelet, proteins include at least one isoform of alpha-tropomyosin containing exon 1a and at least two platelet proteins selected from monoamine oxidase-B, coagulation factor XIIIa, wild-type glutathione S-transferase omega-1 (GSTO-1) or mutant GSTO-1 having an aspartic acid at position 140, wherein if there are no alleles of ApoE4 in the patient's genome then the expression level of wild-type GSTO-1 is determined in step (ii) and if there are one or two alleles of ApoE4 in the patient's genome then the expression level of mutant GSTO-1 is determined in step (ii), wherein the determining of part (ii) comprises contacting the platelet sample from the patient with a solid support comprising one or more antibodies that specifically bind to at least one isoform of alpha-tropomyosin containing exon 1a, and one or more ligands that specifically bind to at least two platelet proteins selected from monoamine oxidase-B, coagulation factor XIIIa, wild-type glutathione S-transferase omega-1 (GSTO-1) protein and/or mutant GSTO-1 protein immobilized thereon, and
(iii) comparing the resulting value of step (ii) to a control value, wherein a result higher than the control value is indicative of Alzheimer's disease.
2. A method according to claim 1 , wherein the at least one isoform of alpha-tropomyosin containing exon 1a is selected from one or more of S1855, S1827, S1896 and S1941.
3. A method according to claim 2 , wherein the at least one isoform of alpha-tropomyosin is S1855.
4. A method according to claim 2 , wherein the expression level of at least one isoform of alpha-tropomyosin containing exon 1a is calculated as the sum of the expression of each of the isoforms S1855, S1827, S1896 and S1941.
5. A method according to claim 1 , wherein the expression level of monoamine oxidase-B is determined in step (ii) of claim 1 .
6. A method according to claim 1 , wherein step (ii) further comprises determining the expression level of ApoE4 protein and/or total ApoE protein in the platelet sample.
7. The method of claim 1 , wherein the at least three antibodies that bind platelet proteins bind to alpha-tropomyosin isoform containing exon 1a, monoamine oxidase B (MAO-B) and wild-type glutathione S-transferase omega-1 (wtGSTO-1).