CD45 isoform alteration in CD4+ T cells as a potential diagnostic marker in alzheimer's disease

Abstract

CD45 isoform switching from the CD45RA to the CD45RO isoform is an indicator of peripheral CD4+ T lymphocyte function, as well as other blood cells. CD45 isoforms are altered on blood cells from AD patients compared to controls, showing significantly lower levels of CD45RA, and an increase in the CD45RO/CD45RA ratio compared to age-matched normal participants. The invention includes a method of assessing the risk of developing, of diagnosing, or of measuring the progression of Alzheimer's disease in a patient comprising of obtaining a blood sample from a patient, determining CD45 isoform expression of blood cells contained in the blood sample, and relating the determined CD45 isoform expression to an assessment of the risk of developing the disease, a diagnosis of the disease, or a measure of the progression of the disease. The blood cells, for purposes of illustration and not limitation, may comprise monocytes, macrophages, lymphocytes, or combinations thereof. In a particular embodiment, the blood cells may comprise T cells, B cells, or a combination thereof. The CD45 isoform may comprise CD45RA, CD45RO, or a combination thereof. The method of the invention may further comprise determining CD45 isoform expression by cytometric analysis, quantitative Western immunoblotting, or quantitative RT-PCR or combinations thereof. The method of the invention may even further comprise determining the APOE genotype or phenotype and relating that APOE genotype or phenotype to the determined CD45 isoform expression to arrive at an assessment of the risk of developing the disease, a diagnosis of the disease, or a measure of the progression of the disease. Another method involves assessing the cognitive status of a patient comprising of obtaining a blood sample from a patient, determining CD45 isoform expression of blood cells contained in the blood sample, and relating the determined CD45 isoform

What is claimed:  
     
         1 . A method of assessing the risk of developing, of diagnosing, or of measuring the progression of Alzheimer's disease in a patient comprising: 
 (i) obtaining a blood sample from a patient;    (ii) determining CD45 isoform expression of blood cells contained in the blood sample; and    (iii) relating the determined CD45 isoform expression to an assessment of the risk of developing the disease, a diagnosis of the disease, or a measure of the progression of the disease.    
     
     
         2 . The method of  claim 1  in which the blood cells comprise monocytes, macrophages, lymphocytes, or combinations thereof.  
     
     
         3 . The method of  claim 1  in which the blood cells comprise T cells, B cells, or a combination thereof.  
     
     
         4 . The method of  claim 1  in which the blood cells comprise CD4+ T cells, CD8+ T cells, or a combination thereof.  
     
     
         5 . The method of  claim 1  in which the CD45 isoform comprises CD45RA, CD45RO, or a combination thereof.  
     
     
         6 . The method of  claim 1  which further comprises determining a ratio of CD45RO isoform expression to CD45RA isoform expression.  
     
     
         7 . The method of  claim 1  in which CD45 isoform expression is determined by cytometric analysis, Western blot, RT-PCR, or a combination thereof.  
     
     
         8 . The method of  claim 1  which is directed to assessing the risk of developing the disease.  
     
     
         9 . The method of  claim 8  in which the relating step comprises comparing the determined CD45 isoform expression to that found in cognitively abnormal patients, cognitively normal individuals, Alzheimer's patients, and patients with other dementias or a combination thereof.  
     
     
         10 . The method of  claim 1  which is directed to diagnosing the disease.  
     
     
         11 . The method of  claim 10  in which the relating step comprises comparing the determined CD45 isoform expression to that found in cognitively abnormal patients, cognitively normal individuals, Alzheimer's patients, and patients with other dementias or a combination thereof.  
     
     
         12 . The method of  claim 1  which is directed to measuring the progression of the disease.  
     
     
         13 . The method of  claim 12  in which the relating step comprises comparing the determined CD45 isoform expression to that found in cognitively abnormal patients, cognitively normal individuals, Alzheimer's patients, and patients with other dementias or a combination thereof.  
     
     
         14 . The method of  claim 1  which further comprises determining APOE genotype or phenotype of the patient.  
     
     
         15 . The method of  claim 14  in which the determined APOE genotype or phenotype is further related to the determined CD45 isoform expression to arrive at an assessment of the risk of developing the disease, a diagnosis of the disease, or a measure of the progression of the disease.  
     
     
         16 . The method of  claim 15  in which the further relating step comprises comparing the determined APOE genotype or phenotype and CD45 isoform expression to that found in cognitively abnormal patients, cognitively normal individuals, Alzheimer's patients, and patients with other dementias or a combination thereof.  
     
     
         17 . A method of assessing the cognitive status of a patient comprising: 
 (i) obtaining a blood sample from a patient;    (ii) determining CD45 isoform expression of blood cells contained in the blood sample; and    (iii) relating the determined CD45 isoform expression to the cognitive status of the patient.    
     
     
         18 . The method of  claim 17  in which the patient is assessed to have a normal cognitive status.  
     
     
         19 . The method of  claim 17  in which the patient is assessed to have an abnormal cognitive status.  
     
     
         20 . The method of  claim 17  in which the relating step comprises comparing the determined CD45 isoform expression to that found in cognitively abnormal patients, cognitively normal individuals, Alzheimer's patients, and patients with other dementias or a combination thereof.