Methods for decreasing beta amyloid protein

Abstract

Blood cholesterol levels are correlated with production of amyloid β protein (Aβ), and are predictors of populations at risk of developing AD. Methods for lowering blood cholesterol levels can be used to decrease production of Aβ, thereby decreasing the risk of developing AD. The same methods and compositions can also be used for treating individuals diagnosed with AD. Methods include administration of compounds which increase uptake of cholesterol by the liver, such as the administration of HMG CoA reductase inhibitors, administration of compounds which block endogenous cholesterol production, such as administration of HMG CoA reductase inhibitors, administration of compositions which prevent uptake of dietary cholesterol, and administration of combinations of any of these which are effective to lower blood cholesterol levels. Methods have also been developed to predict populations at risk, based on the role of cholesterol in production of Aβ. For example, individuals with Apo E4 and high cholesterol, defined as a blood cholesterol level of greater than 200 mg/dl, post menopausal women with high cholesterol levels—especially those who are not taking estrogen, or individuals which high blood cholesterol levels who are not obese are all at risk of developing AD if blood cholesterol levels are not decreased.

1 - 29 . (canceled)  
   
   
       30 . A method for determining if a cholesterol lowering drug composition decreases Aβ production comprising administering a composition which decreases blood cholesterol levels to cells or an animal which can produce Aβ and measuring the production of the Aβ relative to a control not administered the composition.  
   
   
       31 . The method of  claim 30  wherein the composition comprises an HMG CoA reductase inhibitor.  
   
   
       32 . The method of  claim 31  wherein the inhibitor is selected from the group consisting of lovastatin, simvastatin, fluvastatin, pravastatin, atorvastatin, cerivastatin, and compactin.  
   
   
       33 . The method of  claim 30  wherein the composition comprises a compound which inhibits uptake of dietary cholesterol.  
   
   
       34 . The method of  claim 30  wherein the composition blocks or decreases endogenous cholesterol production.  
   
   
       35 . The method of  claim 30  wherein the composition comprises an inhibitor of the cholesterol biosynthetic enzymes selected from the group consisting of 2,3-oxidosqualene cyclase, squalene synthase, and 7-dehydrocholesterol reductase.  
   
   
       36 . The method of  claim 30  wherein the composition is selected from the group consisting of a fibrate, a bile acid binding resin, probucol, nicotinic acid, garlic or garlic derivative, and psyllium.  
   
   
       37 . The method of  claim 30  further comprising determining the effective dosage range of the composition.