Diagnostic method for multiple sclerosis

Abstract

A method of detecting the presence, or monitoring the severity of a condition characterised by the presence of fragments of a marker protein in the brain of a patient. The method comprises: (i) providing a sample comprising macrophages obtained from the patient; and (ii) detecting the presence of the marker protein or fragments thereof in the macrophages. The presence of abnormal levels of the marker protein and/or fragments thereof in the macrophages is indicative of the presence of the condition in the patient. The condition and the marker proteins can be: Alzheimer's Disease and the Abeta peptide, Parkinson's Disease and ubiquitin, Multiple Sclerosis and myelin basic protein, FrontoTemporal Dementia and tau, Amyotrophic Lateral Sclerosis and tau, Parkinson's disease, Lewy Body dementia or Alzheimer's Disease and alpha-synuclein.

1 - 35 . (canceled) 
     
     
         36 . A method of detecting the presence of or monitoring the severity of a disease condition in a patient comprising:
 providing a blood or cerebro-spinal fluid (CSF) sample from the patient; and   detecting the presence of (1) a marker protein or fragments of the marker protein in activated macrophages of the blood or CSF sample and (2) the presence of an additional marker specifically in the blood or CSF sample, wherein both abnormal levels of the marker protein or fragments of the marker protein in the activated macrophages and the presence of the additional marker in the blood or CSF sample are indicative of the presence of or severity of the disease condition in the patient.   
     
     
         37 . The method of  claim 36 , wherein the marker protein is Ali peptide. 
     
     
         38 . The method of  claim 37 , wherein the disease condition is Alzheimer's Disease. 
     
     
         39 . The method of  claim 38 , wherein the additional marker comprises abnormal levels of Aβ42, Tau, Phospho-Tau, Abeta42/Abeta40 ratio, or combinations thereof, in the CSF sample of the patient. 
     
     
         40 . The method of  claim 38 , wherein the abnormal levels of the additional marker comprise a concentration of Aβ42 in the CSF sample of the patient of less than 550 pg/mL. 
     
     
         41 . The method of  claim 38 , wherein the abnormal levels of the additional marker comprise a concentration of Phospho-Tau in the CSF sample of the patient of greater than 85 pg/mL. 
     
     
         42 . The method of  claim 38 , wherein the abnormal levels of the additional marker comprise a concentration ten times the Abeta42/Abeta40 ratio in the CSF sample of the patient of less than one. 
     
     
         43 . The method of  claim 36 , further comprising comparing the levels of the marker protein or fragments of the marker protein with a standard level, the standard level being an average of the levels of the marker protein or fragments of the marker protein in macrophages obtained from a plurality of individuals without the condition, wherein the levels of the marker protein or fragments of the marker protein are abnormal if there is a statistically significant difference from the standard level. 
     
     
         44 . The method of  claim 36 , wherein the disease condition is Parkinson's Disease, Multiple Sclerosis, FrontoTemporal Dementia, or Amyotrophic Lateral Sclerosis. 
     
     
         45 . The method of  claim 36 , wherein the marker protein is ubiquitin, myelin basic protein, tau protein, or alpha-synuclein. 
     
     
         46 . A method of detecting the presence of or monitoring the severity of a disease condition in a patient comprising:
 providing a cerebro-spinal fluid (CSF) or a blood sample from the patient; and   detecting the presence of (1) a marker protein or fragments of the marker protein in activated macrophages of the blood or CSF sample and (2) the presence of an additional marker specifically in an RNA profile of blood or CSF obtained from the patient, wherein both abnormal levels of the marker protein or fragments of the marker protein in the activated macrophages and the presence of the additional marker in the RNA profile are indicative of the presence of or severity of the disease condition in the patient.   
     
     
         47 . The method of  claim 46 , wherein the marker protein is Aβ peptide. 
     
     
         48 . The method of  claim 47 , wherein the disease condition is Alzheimer's Disease. 
     
     
         49 . The method of  claim 48 , wherein the additional marker comprises abnormal levels of Aβ42, Tau, Phospho-Tau, Abeta42/Abeta40 ratio, or combinations thereof, in the CSF sample of the patient. 
     
     
         50 . The method of  claim 48 , wherein the abnormal levels of the additional marker comprise a concentration of Aβ42 in the RNA profile of the patient of less than 550 pg/mL. 
     
     
         51 . The method of  claim 48 , wherein the abnormal levels of the additional marker comprise a concentration of Phospho-Tau in the RNA profile of the patient of greater than 85 pg/mL. 
     
     
         52 . The method of  claim 48 , wherein the abnormal levels of the additional marker comprise a concentration ten times the Abeta42/Abeta40 ratio in the RNA profile of the patient of less than one. 
     
     
         53 . The method of  claim 46 , further comprising comparing the levels of the marker protein or fragments of the marker protein with a standard level, the standard level being an average of the levels of the marker protein or fragments of the marker protein in macrophages obtained from a plurality of individuals without the condition, wherein the levels of the marker protein or fragments of the marker protein are abnormal if there is a statistically significant difference from the standard level. 
     
     
         54 . The method of  claim 46 , wherein the disease condition is Parkinson's Disease, Multiple Sclerosis, FrontoTemporal Dementia, or Amyotrophic Lateral Sclerosis. 
     
     
         55 . The method of  claim 46 , wherein the marker protein is ubiquitin, myelin basic protein, tau protein, or alpha-synuclein.