Isolated components of dense microspheres derived from mammalian brain tissue and antibodies thereto

Abstract

DMS present in the brain of individuals susceptible to cerebral amyloidosis disintegrate into DMS components to form cerebral amyloid plaques and other DMS components that are removed from the brain via circulating bodily fluids. Detecting the presence of these removed DMS components and/or antibodies thereto in circulating bodily fluids provides a diagnostic mechanism to determine the onset of cerebral amyloid plaque formation. Detecting the presence of these removed DMS components and/or antibodies thereto in circulating bodily fluids also provides a diagnostic mechanism to determine the efficacy of treatment regimes for preventing cerebral amyloid plaque formation. Antibodies also can be raised against isolated DMS components and subsequently utilized in a diagnostic method capable of detecting the onset of cerebral amyloid plaque formation.

1 . A composition of matter consisting essentially of at least one dense microsphere (DMS) component having a molecular weight selected from the group consisting of 25-27, 28-30, 45-47, 50-53, 55-57, 60-65 and 76-80 kilodaltons.  
     
     
         2 . A composition according to  claim 1 , wherein said at least one component is a membrane component.  
     
     
         3 . A component according to  claim 1 , that is the product of a process comprising the steps of 
 (a) obtaining a sample of cerebrospinal fluid from a mammal susceptible to or suffering from Alzheimer's disease to provide a solution comprising DMS components;    (b) separating the DMS components in the solution on a gel by polyacrylamide gel electrophoresis; and then    (c) isolating a band that corresponds to a component, wherein said bane is located at a kilodalton region of said gel selected from the group consisting of 25-27, 28-30, 45-47, 50-53, 55-57, 60-65 and 76-80 kilodaltons.    
     
     
         4 . A composition consisting essentially of antibody which specifically binds an isolated component of DMS according to  claim 1 .  
     
     
         5 . A method for diagnosing cerebral plaque formation, Alzheimer's disease and related conditions, comprising the steps of 
 (a) bringing a biological sample into contact with a first antibody directed against at least one component of DMS having a molecular weight selected from the group consisting of 25-27, 28-30, 45-47, 50-53, 55-57, 60-65 and 76-80; and    (b) determining whether said first antibody reacts immunologically with said biological sample.    
     
     
         6 . A method according to  claim 5 , wherein step (b) comprises the steps of 
 (i) reacting said first antibody with said sample to form antibody/component complexes;    (ii) washing said sample to remove any unbound first antibody;    (iii) contacting said sample of step (ii) with a labelled second antibody which binds specifically to said first antibody;    (iv) washing said sample of step (iii) to remove any unbound labelled second antibody; and then    (v) detecting the presence of bound labelled second antibody.    
     
     
         7 . A composition of matter consisting essentially of at least one dense microsphere (DMS) component having a molecular weight selected from the group consisting of 55-60, 62-70 and 82-90 kilodaltons.  
     
     
         8 . A composition according to  claim 7 , wherein said at least one component is a membrane component.  
     
     
         9 . A component according to  claim 7 , that is the product of a process comprising the steps of 
 (a) obtaining a sample of cerebrospinal fluid from a mammal susceptible to or suffering from Alzheimer's disease to provide a solution comprising DMS components;    (b) separating the DMS components in the solution on a gel by polyacrylamide gel electrophoresis; and then    (c) isolating a band that corresponds to a component, wherein said bane is located at a kilodalton region of said gel selected from the group consisting of 55-60, 62-70 and 82-90 kilodaltons.    
     
     
         10 . A composition consisting essentially of antibody which specifically binds an isolated component of DMS according to  claim 7 .  
     
     
         11 . A method for diagnosing cerebral plaque formation, Alzheimer's disease and related conditions, comprising the steps of 
 (a) bringing a biological sample into contact with at least one component of DMS having a molecular weight of 55-60, 62-70 and 82-90 kilodaltons; and then    (b) determining whether said component reacts immunologically with said biological sample.    
     
     
         12 . A method according to  claim 11 , wherein step (b) comprises the steps of 
 (i) washing said sample to remove any unbound components;    (ii) contacting a first antibody which is present in said sample, said first antibody being bound to said component, with a labelled second antibody which binds specifically to said first antibody;    (iii) washing said sample to remove any unbound second antibody; and then    (iv) detecting the presence of bound second antibody.    
     
     
         13 . A composition of matter comprising a compound and a pharmaceutically acceptable vehicle wherein said compound is effective in decreasing the type and concentration of at least one DMS component or anti-DMS antibody in cerebrospinal fluid when administered to a mammal susceptible to or suffering from Alzheimer's disease.  
     
     
         14 . A method of preventing the formation of cerebral amyloid plaque, inhibiting the disruption of DMS in the brain of a mammal or treating a mammal susceptible to or suffering from Alzheimer s disease comprising administering to said mammal a therapeutically effective amount of a composition as claimed in  claim 13  for a therapeutically effective period of time.  
     
     
         15 . The method as claimed in  claim 14 , wherein said composition is administered periodically.