Kits for determining risk of Alzheimer's disease

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

We claim:  
     
         1 . A method for decreasing the production of Aβ comprising administering a composition which decreases blood cholesterol levels to a person with elevated cholesterol levels who is at risk of, or exhibits the symptoms of, Alzheimer's disease.  
     
     
         2 . The method of  claim 1  wherein the composition is an HMG CoA reductase inhibitor.  
     
     
         3 . The method of  claim 2  wherein the composition is selected from the group consisting of lovastatin, simvastatin, fluvastatin, pravastatin, atorvastatin, cerivastatin, and compactin.  
     
     
         4 . The method of  claim 1  wherein the composition inhibits uptake of dietary cholesterol.  
     
     
         5 . The method of  claim 1  wherein the composition blocks or decreases endogenous cholesterol production.  
     
     
         6 . The method of  claim 1  wherein composition increases cholesterol metabolism or clearance.  
     
     
         7 . The method of  claim 1  wherein the person carries the apolipoprotein E4 gene.  
     
     
         8 . The method of  claim 1  wherein the person has trisomy 21 (Down's syndrome).  
     
     
         9 . The method of  claim 1  wherein the person carries one or more mutations in the genes that encode amyloid β protein, amyloid precursor protein, presenilin-1 or presenilin-2.  
     
     
         10 . The method of  claim 1  wherein the person has a family history of Alzheimer's disease or dementing illness.  
     
     
         11 . The method of  claim 1  wherein the person is a post menopausal woman with high cholesterol.  
     
     
         12 . The method of  claim 1  wherein the person has high blood cholesterol levels who is not obese.  
     
     
         13 . The method of  claim 1  wherein the person is between 48-65 years of age.  
     
     
         14 . A method for predicting if a person is at risk of developing Alzheimer's Disease comprising determining if they have elevated blood levels of cholesterol.  
     
     
         15 . The method of  claim 14  wherein the level is 200 mg/dl or greater.  
     
     
         16 . The method of  claim 14  further comprising determining if the person carries the apolipoprotein E4 gene.  
     
     
         17 . The method of  claim 14  further comprising determining if the person has trisomy  21  (Down's syndrome).  
     
     
         18 . The method of  claim 14  further comprising determining if the person carries one or more mutations in the genes that encode amyloid β protein, amyloid precursor protein, presenilin-1 or presenilin-2.  
     
     
         19 . The method of  claim 14  further comprising determining if the person has a family history of Alzheimer's disease or dementing illness.  
     
     
         20 . The method of  claim 14  further comprising determining if the person is a post menopausal woman with high cholesterol.  
     
     
         21 . A kit for determining if a person is at risk of developing Alzheimer's disease comprising reagents for determining if the blood cholesterol level is in excess of 200 mg/dl.  
     
     
         22 . The kit of  claim 21  further comprising reagents for determining at least one of the factors selected from the group consisting of the apolipoprotein E4 gene or its product, amyloid β protein, amyloid precursor protein, presenilin-1, and presenilin-2.  
     
     
         23 . A composition for decreasing the production of Aβ comprising an effective amount of a compound to decrease blood cholesterol levels.  
     
     
         24 . The composition of  claim 23  comprising an HMG CoA reductase inhibitor.  
     
     
         25 . The composition of  claim 24  wherein the inhibitor is selected from the group consisting of lovastatin, simvastatin, fluvastatin, pravastatin, atorvastatin, cerivastatin, and compactin.  
     
     
         26 . The composition of  claim 23  comprising a compound which inhibits uptake of dietary cholesterol.  
     
     
         27 . The composition of  claim 23  wherein the composition blocks or decreases endogenous cholesterol production.  
     
     
         28 . The composition of  claim 27  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.  
     
     
         29 . The composition of  claim 23  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.